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OF  CALIFORNIA 

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Dr.  William  Adams 


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BLOOD  TRANSFUSION 

HEMORRHAGE  AND 

THE  ANiEMIAS 


BY 
BERTRAM  M.fiERNHEIM,  A.B.,  M.D.,  RA.C.G. 

INSTBUCTOB    IN    CLINICAL  8T7BGEBT,  THE  JOHNS  HOPKINS  UNIVER8ITT,  CAPTAIN,  MEDICAL 

CFriCEBS'    BESEBTE   CORPS,   TJ.   S.    A.,  AUTHOR  OV   "SURQERT  OF 

THE  TABCULAR  BT8TEM,"    ETC. 


PHILADELPHIA  AND  LONDON 

J.  B.   LIPPINCOTT  COMPANY 


COFTBIQHT,  Ifll?,  BT  J.  B.  I4IPPINCOTT  COMPANT 


Bltctrotyped  and  pHnttd  by  J.  B.  LiPPincotl  Company 
The  Washington  Square  Press,  Philadelphia,  U.S.A. 


TO 
H.  M  B. 


819512 


PREFACE 

The  present  volume  is  an  outgrowth  of  a  chapter  on 
Blood  Transfusion  written  in  1913  as  part  of  a  mono- 
graph published  in  that  year  on  Surgery  of  the  Vascu- 
lar System.  After  a  very  gratifying  distribution  of 
that  work,  a  revision  seemed  in  order  because  of  the 
many  advances  made  in  this  field  of  surgery,  but  on 
addressing  myself  to  the  task,  I  was  amazed  at  the 
development  attained  by  the  subject  of  transfusion 
to  which  just  one  chapter  had  been  devoted  only  a 
short  time  before.  Such  revolutionary  changes  in 
technic  had  come  about  and  the  usefulness  of  trans- 
fusion had  developed  so  tremendously  that  it  seemed 
wise  to  postpone  the  contemplated  revision,  and  to 
prepare  a  separate  work  with  the  single  topic  of  blood 
transfusion.  An  enormous  amount  of  work  has  been 
carried  out  in  recent  years  by  hundreds  of  enthusiastic 
investigators  as  a  result  of  which  a  vast  literature  has 
arisen,  still  there  has  been  no  compilation  of  the  sub- 
ject since  Crile's  work  on  "  Hemorrhage  and  Trans- 
fusion "  in  1909,  before  transfusion  had  proved  itself 
of  practical,  enduring  worth. 

Crile's  stimulating  book  was  devoted  mainly  to  the 
experimental  aspect  of  transfusion,  although  its  clini- 


vi  PREFACE 

cal  side  was  considered  as  far  as  was  possible  at  that 
time.  The  book  has  never  been  revised  for  reasons  best 
known  to  its  author,  but  the  probabilities  are  that, 
having  pointed  the  way,  Dr.  Crile's  interests  led  him 
into  other  fields.  iJnder  these  circumstances,  it  seemed 
that  a  compilation  setting  forth  all  the  various  methods 
of  the  present  day,  with  a  consideration  of  the  indica- 
tions for  transfusion,  and  a  brief  appendix  containing 
pre-transf usion  tests  might  be  timely. 

It  has  been  my  purpose  to  adhere  to  the  practical 
side  of  the  subject,  both  as  regards  discussions  of  indi- 
cations, atid  selection  of  transfusion  methods.  Theo- 
retical considerations  have  been  eliminated  as  far  as 
possible,  and  the  future  uses  to  which  blood  transfu- 
sion may  be  put  have  hardly  been  suggested,  since 
the  book  is  meant  for  the  man  who  is  engaged  in  clini- 
cal work  of  this  nature,  and  desires  to  know  concretely 
what  is  being  done  and  how  to  do  it.  Those  interested 
in  the  laboratory  side  of  blood  work  are  referred  to  the 
abimdant  literature,  references  to  which  have  been 
selected  with  utmost  care,  in  regard  to  both  the  clinical 
problems  and  the  abstract  phases  of  the  subject. 

Bertram  M.  Bernheim. 
2313  EuTAW  Place, 

Baltimore,  Maeyland. 

May,  1917. 


FOREWORD 

It  is  due  to  the  author  of  this  work  to  state  that 
his  sudden  departure  for  foreign  war  service  as  a  mem- 
ber of  the  Johns  Hopkins  Base  Hospital  Unit,  has 
caused  his  treatise  to  be  issued  without  opportunity 
for  his  final  inspection  and  revision.  Under  these  con- 
ditions indulgence  is  requested  for  some  omissions  and 
inadvertences  which  would  have  been  corrected  under 
normal  circumstances. 

J.  B.  LiPPiNcoTT  Company. 


HISTORICAL  NOTE 

Investigation  of  early  records  indicates  quite 
clearly  that  the  inherent  possibility  for  benefit  from 
blood  trajisfusion  was  recognized  hundreds  of  years 
ago,  and  bona  fide  attempts  to  carry  out  the  procedure 
are  noted  as  early  as  1492,  when  a  transfusion  failed 
to  save  the  life  of  Pope  Innocent  VIII.  Three  youths 
are  said  to  have  lost  their  lives  as  a  result  of  the  trial. 
Following  this,  sporadic  transfusions  are  found,  nota- 
bly one  in  1667,  by  Jean  Baptiste  Denys,  physician 
to  Louis  XIV.  And  it  was  about  this  time  that 
Richard  Lower,  a  physiologist,  devised  a  practical 
method  of  direct  transfusion  almost  identical  with  one 
the  author  thought  he  had  originated  about  two  hun- 
dred and  fifty  years  afterwards !  Lower  conceived  the 
idea  of  running  blood  from  the  vessels  of  one  indi- 
vidual into  those  of  another  by  means  of  two  or  more 
segments  of  goose  quills  interposed  between  the  sev- 
ered ends  of  the  vessels,  while  the  author  accomplished 
the  same  purpose  by  means  of  a  two-pieced  silver  tube 
as  portrayed  on  page  97. 

The  trials  of  the  early  years  are  interesting  as  in- 
dicators of  the  modern  trend  of  thought,  but  furnish 
little  of  value  concerning  actual  blood  transfusion 


X  HISTORICAL  NOTE 

because  the  idea  was  too  far  in  advance  of  anatomical 
and  surgical  knowledge  and  practice  of  the  times. 
Harvey's  discovery  of  the  circulation  of  the  blood  did 
not  appear  in  print  till  1628,  so  there  is  little  wonder 
that  progress  in  a  matter  so  intimately  dependent  on 
knowledge  of  the  circulation  was  delayed  and  uncer- 
tain. Not  until  1892  was  any  real  progress  made.  At 
this  time  Von  Ziemssen  reported  on  a  method  of  in- 
direct blood  transfer  by  means  of  needle  and  syringes, 
which  was  of  some  practical  utility  though  it  was  far 
from  satisfactory.  His  method  made  little  impression, 
fell  into  disuse,  and  little  was  heard  of  it  till  some 
twenty  or  more  years  later  when  it  was  revived  and 
perfected  by  Dr.  Edward  Lindeman,  with  whose 
name  the  method  is  now  associated. 

In  reality  the  history  of  blood  transfusion  can  be 
divided  into  four  rather  sharply  defined  divisions 
which  are  as  follows : 

First:  That  of  the  early  abortive,  sporadic  at- 
tempts, the  period  dating  from  the  year  1492  with  the 
historic  transfusion  carried  out  in  the  effort  to  save 
the  life  of  Pope  Innocent  VIII,  to  Carrel's  work  on 
the  blood  vessels,  which  marked  a  turning  point. 

Second:  The  truly  epoch-making  experiments  of 
Carrel  in  which  he  devised  the  present  day  technic  of 
handling  blood  vessels,  and  paved  the  way  for  Crile's 
work  on  blood  transfusion.    To  Dr.  George  W.  Crile, 


HISTORICAL  NOTE  xi 

of  Cleveland,  must  go  the  credit  for  having  devised  and 
perfected  the  first  practical  method  of  carrying  out 
this  operation,  and  for  having  by  this  method 
awakened  renewed  interest  in  a  procedure,  long  dis- 
carded because  of  the  impossibility  of  securing  an  accu- 
rate blood  transfer. 

This  second  period  may  be  designated  the  period 
of  Direct  Transfusion,  for  Crile's  work  incited  many 
who  enthusiastically  set  to  work  and  in  short  order 
devised  various  ingenious  instruments,  all  calculated 
to  facilitate  and  simplify  the  direct  flow  of  blood  from 
one  individual  to  another.  Crile's  little  tube  was  early 
overshadowed  because,  though  quite  practical  and  con- 
stant in  its  results,  it  demanded»a  degree  of  skill  for  its 
proper  handling  that  was  found  unnecessary  for  the 
successful  use  of  subsequently  contrived  instruments. 
The  names  of  Carrel,  Payr,  Crile,  Elsberg,  Brewer, 
Ottenberg,  Levin,  Lespinasse,  Soresi  and  many  others 
are  linked  vnth  this  period  to  whose  development  the 
author  hopes  he  is  not  presumptuous  in  venturing  to 
believe  that  he  contributed  a  share. 

The  Third  Period  is  that  of  Indirect  Transfusion 
of  whole  blood,  and  dates  from  Lindeman's  revival 
in  1913  of  Von  Ziemssen's  old  method.  Other  methods 
such  as  that  of  Cmiis  and  David  had  been  suggested 
for  indirect  transfusion  prior  to  Lindeman's  report,  but 
it  must  be  granted  that  this  method  foimd  little  favor 


xii  HISTORICAL  NOTE 

until  the  needle  and  syringe  system  came  into  vogue — 
and  then  it  gradually  became  the  method  of  election. 
The  reason  for  its  popularity  was  that,  in  addition 
to  requiring  very  small  incisions  or  (in  certain  in- 
stances) none  at  all,  the  amount  of  blood  could  be 
accurately  measured — an  impossibility  by  any  of  the 
methods  of  direct  transfusion  extant.  Modifications 
of  Lindeman's  suggestion  have  been  many  and  diverse 
and  several  are  far  simpler  than  his  in  their  execution. 
The  chief  workers  of  this  period  are  Lindeman, 
Unger,  Miller,  Kimpton  and  Brown,  Satterlee  and 
Hooker,  Vincent,  Percy  and  a  host  of  others  among 
whom  the  author  again  craves  permission  to  include 
himself.  The  instruments  these  men  perfected  are 
responsible  in  great  measure  for  the  rapid  develop- 
ment of  transfusion  and  its  growing  popularity  as  a 
reliable  therapeutic  measure. 

Beside  the  increased  knowledge  concerning  the 
technic  of  blood  transfusion,  the  third  period  is  also 
notable  for  the  general  recognition  it  inaugurated  of 
the  necessity  for  carrying  out  tests  for  haemolysis 
and  agglutination  prior  to  transfusion,  and  for  the  de- 
velopment of  the  requisite  tests.  With  this  work 
Moss'  name  is  closely  linked  since  he  first  showed 
that  practically  all  people  may  be  divided  into  four 
groups  as  regards  their  blood  and  that  only  those 
should  serve  as  donors  whose  blood  is  in  the  same 


HISTORICAL  NOTE  xiii 

group  as  that  of  the  recipient.  Ottenberg  and  Kaliski, 
Epstein  and  Ottenberg,  Vincent,  Whipple,  Hess, 
Brem,  Minot  and  others  also  did  work  along  these 
and  related  lines,  some  of  which  was  carried  out  before 
the  beginning  of  the  Thu*d  Period.  But  the  real  fun- 
damental importance  of  the  subject  was  unfortunately 
delayed  until  the  increasing  facility  for  carrying  out 
transfusions  gave  rise  to  an  increasing  number  of 
accidents  that  were  shown  to  be  due  to  a  failure 
properly  to  group  those  participating  in  the  operation. 
The  Fourth  Period  is  just  beginning  and  may  well 
be  termed  the  Period  of  Anticoagulation  or  Indirect 
Transfusion  with  the  Aid  of  Anticoagulants.  The 
desirability  of  having  blood  in  an  uncoagulable  state 
has  long  been  uppermost  in  the  minds  of  those  most 
intimately  acquainted  with  transfusion  problems,  and 
the  sporadic  attempts  to  use  defibrinated  blood  may  be 
taken  as  manifestations  of  this  feeling.  But  defibri- 
nated blood  proved  a  dismal  failure  and  anticoaggu- 
lants  of  a  chemical  nature  were  always  considered  un- 
suitable for  practical  purposes  because  of  their  well- 
known  toxic  properties.  Thus  matters  rested  until  in 
1913-14  the  work  of  Dr.  John  Abel,  the  well-known 
Pharmacologist,  on  Plasmapheresis  caused  renewed 
interest  in  this  phase  of  the  subject  by  demonstrating 
the  efficacy  of  hirudin  in  preventing  blood  coagulation 
in  the  dog  without  harmful  effects.    Following  this,  in 


xiv  HISTORICAL  NOTE 

1914,  Satterlee  and  Hooker  reported  on  an  ingenious 
and  safe  method  of  using  hirudin  for  human  trans- 
fusions, but  the  method  never  became  popular  because 
of  the  rather  cumbersome  technic  and  because  of  the 
known  toxicity  of  hirudin.  And  in  addition  com- 
mercial preparations  of  the  substance  have  always 
been  rather  unreliable. 

Thus,  little  real  progress  toward  the  widespread  use 
of  anticoagulants  was  made,  until  the  work  of  Hustin, 
Weil,  Lewisohn  and  Agote,  in  1915,  rather  unex- 
pectedly placed  the  method  on  a  firm  footing.  All 
four  of  these  men,  working  independently  of  each 
other,  came  to  the  conclusion  that  sodium  citrate,  long 
known  to  pharmacologists  for  its  anticoagulant  prop- 
erties, could  be  used  in  the  human  with  perfect  safety 
provided  care  was  exercised  in  securing  the  proper 
dilution.  Elaborate  experiments  on  animals  proved 
the  correctness  of  their  contention  and  now  the  sodimn 
citrate  method  of  indirect  transfusion  of  blood  bids 
fair  to  supplant  all  previously  known  methods. 

Thus,  the  procedure  of  blood  transfusion  has 
evolved  in  successive  stages  from  an  undertaking  of 
the  most  difficult  and  dangerous  character,  resorted  to 
upon  the  rarest  occasions,  to  a  procedure  of  such 
simple  and  harmless  character  that  it  is  utilized 
throughout  the  civilized  world  many,  many  times  each 
day.     Hundreds  of  people  have  been  saved  from 


HISTORICAL  NOTE  xv 

premature  death  from  haemorrhage,  and  the  number 
of  conditions  in  which  it  is  utilized  for  therapeutic 
benefit  is  constantly  increasing.  Still,  we  are  only  on 
the  threshhold  of  knowledge  concerning  the  funda- 
mental character  of  the  procedure,  and  the  uses  to 
which  it  will  eventually  be  put.  Even  now  studies  are 
in  progress,  and  cases  have  been  done  with  gratifying 
results,  where  only  the  cellular  content  of  the  blood 
has  been  used,  an  outgrowth  of  blood  transfusion  that 
could  have  come  about  only  through  the  use  of  anti- 
coagulants, and  one  that  may  prove  to  be  of  far- 
reaching  import. 


CONTENTS 


CHAPTER  PAGE 

I.    BlX)OD  AND  THE  PHENOMENON  OF  BlEEDING 1 

II.  Diagnosis  of  Hemorkhage 17 

in.  Control  of  Hemorrhage.    Factors  Involved  in  a  Determina- 
tion OF  Danger  Limits.  Blood  Pressure 34 

IV.  Indications  for  Transfusion 46 

V.  Dangers  of  Transfusion.   Haemolysis  and  Agglutination 53 

-Vl.  Selection  of  Donor  for  Transfusion.     Dangers  to  Donor. 

Treatment  of  Donor  after  Transfusion 77 

VII.  Methods  of  Transfusion.    Technic 87 

VIII.  Transfusion  for  Acute  Hemorrhage  and  Shock.  Accidental 
Gastric  Ulcer.  Post-operative.  Post-partum  Placenta 
Pr^evia.   Extra-Uterine  Pregnancy.   Typhoid  Fever 147 

IX.  Transfusion  for  An^siic  and  Debilitated  Conditions  in  Gen- 
eral.   Blood  Dosage 171 

X.  Primary  Pernicious  Anemia 181 

XI.  Transfusion  for  Hjbmofhilia,  MsLiENA  Neonatorum,  Purpura, 

Jaundice 201 

XII.  Leukemia.  Splenic  An.£uia  (Banti's  Disease)  Certain  Toxae- 
mias   226 


ILLUSTRATIONS 


no.  PAQB 

1.— Crile  Cannula  91 

ft. — Drawing  Vein  Through  Cannula 91 

3. — Cuffing  Vein  Back  Over  the  Cannula 92 

4. — Vein  Cuffed  and  Tied  in  Groove  Nearest  Handle  of  the  Cannula.    Art- 
ery Grasped  by  Three  Mosquito  clamps 92 

5. — Artery  Slipped  Over  Cannula  and  Tied  in  the  Second  Groove.    Anasto- 
mosis Complete 9S 

6. — Elsberg's  Monkey-wrench  Cannula 94 

7. — Artery  "set"  in  Elsberg's  Cannula;  Tenacula  in  Position  for  Cuffing 95 

8. — Artery  Everted  and  Impaled  on  the  Hooka.    Vein  Grasped  by  Mosqui- 
to Clamps 95 

9. — Cannula  Slipped  Into  Side  of  Vein  and  Tied  in  Position.    Anastomosis 

Complete 95 

10. — Author's  Two-pieced  Transfusion  Tube 97 

11. — Bemheim's  Transfusion  of  Blood 102 

12. — ^Tubes  Invaginated  and  Anastomosis  Complete 108 

IS.— Cannulas  (1,  2,  3) 118 

14.— Cannula  (Hollow  Needle) 118 

15. — Unger's  Instrument  for  Indirect  Transfusion 118 

16. — Bemheim's  Method  Syringe 126 

17.— Shows  Use  of  Needle  to  Take  Blood  from  Vein  at  the  Elbow 132 

18. — Shows  Position  of  Infant's  Head  and  Point  at  Which  the  Injection  of 

Blood  is  Made  Into  the  Longitudinal  Sinus 135 


ZIX 


BLOOD  TRANSFUSION, 

HEMORRHAGE  AND 

THE  ANEMIAS 

CHAPTER  I 

BLOOD  AND  THE  PHENOMENON  OF  BLEEDING 

Loss  of  blood  is  such  a  common-place  every-day 
aiFair  in  the  lives  of  most  people  that  its  analytical 
consideration  except  mider  unusual  or  alarming  con- 
ditions might  seem  almost  foolish  were  it  not  for  the 
fact  that  many  features  connected  with  it  are  most 
obscure,  and  its  very  commonness  has  a  tendency  to 
breed  a  degree  of  indifference  that  sometimes  results  in 
disaster.  Confined  in  a  set  of  hollow  elastic  tubes  whose 
calibre  varies  tremendously,  whose  walls  are  so  coarse  in 
certain  localities  as  to  be  able  to  withstand  enormous 
pressure  and  so  delicate  at  other  places  as  to  be  invis- 
ible to  the  naked  eye,  whose  ramifications  penetrate 
to  the  uttermost  limits  of  the  whole  body,  blood  is  a 
constantly  circulating  liquid  of  such  limited  volume 
that  comparatively  small  losses  give  rise  to  profound 
disturbances.  It  is  possessed  of  a  most  remarkable 
property,  that  of  coagulation,  without  which  there 
could  be  no  preservation  of  life,  yet  it  remains  con- 


2  BLOOD  TRANSFUSION 

stantly  fluid  while  within  its  channels,  certain  dis- 
eased states  excepted — and  day  and  night,  year  in 
and  year  out,  instigated  by  the  ceaselessly  beating 
heart,  it  carries  sustenance  throughout  its  domains. 

So  long  as  all  is  well,  scarcely  any  attention  is  paid 
to  it.  Only  derangements  are  worthy  of  notice,  and 
fortune  has  endow^ed  the  blood  with  one  other  quality 
of  such  nature  that  many  and  repeated  insults  are 
borne  with  equanimity,  and  derangements  often  pass 
unnoticed  until  they  have  become  serious — so  serious 
as  to  be  at  times  iiTcparable;  for  in  addition  to  its 
quality  of  fluidity  within  its  channels  and  that  of 
coagulation  outside  of  them,  blood  has  a  still  further 
power — that  of  regeneration,  through  which  means 
losses  are,  under  certain  circumstances,  retrieved. 
Equipped  in  this  tlireefold  manner,  the  blood  is  able 
to  care  for  itself  so  satisfactorily  that  trifling  de- 
rangements pass  imnoticed,  and  even  those  of  greater 
magnitude  frequently  give  little  concern,  a  rather  un- 
fortunate circumstance  from  certain  view-points  be- 
cause it  gives  rise  at  times  to  a  false  security  that  a  more 
sensitive  registering  mechanism  would  not  tolerate. 
If  the  blood  could  notify  us  of  its  minor  disturbances, 
we  would  necessarily  form  the  habit  of  more  frequently 
examining  it,  and  consequently  would  be  able  to  recog- 
nize in  an  early  stage  conditions  which,  under  present 
circLunstances,  are  only  apparent  when  far  advanced. 


THE  PHENOMENON  OF  BLEEDING  3 

Particularly  is  this  true  of  the  anaemias,  affections  so 
slow  in  their  onset  and  so  insidious  that  such  hints  as 
increasing  pallor,  shortness  of  breath,  weakness,  are 
danger  signals  usually  sounded  too  late.  If  there 
were  some  more  m-gent  sign,  we  might  be  of  greater 
service. 

Before  discussing  the  various  kinds  of  hemorrhage, 
it  may  be  well  to  point  out  that  blood  may  be  lost  in 
different  ways,  some  of  which  are  not  serious,  while 
all  are  capable  of  becoming  so,  and  that  the  same  type 
of  bleeding  in  many  cases  may  arise  from  any  one  of 
a  number  of  causes.  So  a  simple  tabulation  of  the 
different  kinds  of  hemorrhage  can  do  but  little  more 
than  concretely  picture  various  possibilities,  the  actual 
diagnosis  of  a  given  condition  depending  mainly  upon 
the  discriminating  powers  and  experience  of  the  phy- 
sician in  charge. 

It  seems  wise  to  divide  hemorrhages  into  two 
classes,  concealed  and  unconcealed,  which  means  that 
all  bleeding  is  either  apparent  to  the  eye,  or  non- 
apparent.  The  intra-abdominal  hemorrhage  from  a 
ruptured  liver  is  an  example  of  the  first,  while  the 
bleeding  from  lacerated  tissues  is  a  type  of  the  latter. 
It  is  obvious  that  both  concealed  and  unconcealed 
blood  loss  may  be  the  result  of  some  accident. 

Pulmonary  hemorrhages  are  always  unconcealed, 
as  are  in  reality  bleedings  from  the  intestinal  tract. 


4  BLOOD  TRANSFUSION 

but  because  it  sometimes  requires  hours  or  days  for 
the  blood  to  pass  out,  this  latter  form  is  usually  cited 
under  both  the  concealed  and  unconcealed  bleedings. 
Uterine  bleedings  must  be  tabulated  as  of  this  sort, 
too,  because  of  the  inability  of  the  blood  to  get  out 
under  certain  conditions,  and  because  of  the  intra- 
abdominal hemorrhage  accompanying  ruptured  extra- 
uterine pregnancy.  In  fact,  nearly  all  bleedings  fall 
under  both  headings,  and  for  similar  reasons.  For 
example,  a  post-operative  hemorrhage  is  apparent, 
depending  upon  whether  or  not  the  wound  has  been 
closed  or  drained,  or  whether  the  drains  have  been 
packed  in  so  tight  as  to  amount  to  a  closure.  Hemor- 
rhage from  the  urinary  system  is  apparent,  if  it  is 
passed,  but  it  is  not  always  passed  and  therefore  re- 
mains concealed  perhaps  until  a  catheter  is  placed  into 
the  bladder.  The  slow  bleedings  resulting  from  de- 
fective coagulation  are  of  both  varieties,  while  intra- 
cranial hemorrhages,  imless  due  to  great  violence,  are 
always  concealed.  The  simple  table  outlined  below 
will  serve  as  an  approximate  guide. 

With  one  exception,  that  of  menstruation,  bleed- 
ing is  a  pathological  process  and  should  always  be 
regarded  as  such,  since  the  blood  can  only  serve  its 
purpose  when  within  its  own  confines.  It  is  possible 
that  the  blood  loss  known  as  menstruation  is  patho- 
logical, but  since  it  occurs  regularly  each  month  dur- 


THE  PHENOMENON  OF  BLEEDING  5 

ing  certain  years  in  the  lives  of  practically  all  women, 
the  conclusion  can  hardly  be  escaped  that  it  is  a  nor- 
mal affair.    Why  it  begins  at  a  definite  period  of  life 


Hehoiuuiage 


CONCEALED 


UNCONCEALED 


I.  Traumatic 
II.  Non-traumatic 

1.  From  the  alimen- 
tary tract 


Nasal 

(Esophageal 

Gastric 

Intestinal 

Rectal 


I.  Traumatic 
II.  Non-traumatic 

1.  From  the  alimen- 
tary tract 


Nasal 

(Esophageal 

Gastric 

Intestinal 

Rectal 


ft.  In  any  of  the 
body  cavi- 


ties or  tis- 
sues 


'  Cranium — ^rup- 
tured blood 
vessel — apo- 
plexy 

Chest   —    rup- 
tured   aneur- 


2.  Pulmonary 


ism 
Abdomen 


Ectopic 
Aneurism 
Ruptured  organ 
^  Ulcer 
Intra-intestinal 
Bladder 


{Separated  placenta 
Ectopic  pregnancy 
Menstruation  retained 


4.  Consequent  upon  defective  co- 
agulation apparatus  (hemor- 
rhagic group) 


3.  Uterine  < 


Menstruation 
Ulcerated  growth 
Pregnancy 
Post  partum 
Placenta  prsevia 
,  Idiopathic 


6.  Post-operative 


4.  Consequent  upon  defective  co- 
agulation apparatus  (hemor- 
rhagic group) 

6.  Post-operative 


and  ceases  at  an  equally  marked  period  may  have  its 
apparent  explanation  in  the  beginning  and  cessation 
of  ovulation,  but  this  fails  to  explain  why  a  true  hemor- 


6  BLOOD  TRANSFUSION 

rhagic  condition  should  necessarily  accompany  ovula- 
tion at  all.  It  must  not  only  be  regarded  as  normal, 
at  present,  but  it  must  be  granted  that  it  causes  little 
or  no  disturbance,  such  as  might  be  expected  in  a 
similar  periodic  loss  of  equal  amounts  of  blood  imder 
other  circumstances.  Its  discussion  in  detail  would 
be  out  of  place  in  a  work  of  this  kind,  except  in  so  far 
as  menstruation  becomes  abnormal  and  causes  dis- 
turbances of  such  character  as  to  require  interference. 
These  will  be  considered  in  their  proper  place. 

Accidental  bleeding  is  of  common  occurrence, 
especially  minor  varieties,  and  usually  gives  rise  to 
little  or  no  anxiety.  The  coagulatory  apparatus  of 
the  blood  comes  to  the  rescue  unbidden  and  usually 
stops  the  leakage  very  promptly.  As  a  consequence, 
a  carelessness  concerning  these  matters  has  arisen  that 
at  times  causes  serious  results,  because  it  occasionally 
happens  that  the  coagulative  powers  of  the  blood  are 
unable  to  check  the  flow  unaided.  Further  experi- 
ence has  shown  that  in  such  cases  the  longer  the  bleed- 
ing continues  the  more  difficult  the  task  of  stopping  it 
becomes.  The  reason  for  this  is  not  clear,  though  the 
attempted  explanation  is  that  a  derangement  of  the 
coagulatory  apparatus  takes  place  and  becomes  pro- 
gressively worse,  though  just  what  this  derangement 
is  or  why  it  should  occur  in  certain  instances  and  not 
in  others,  remains  obscure.    It  is  also  baffling  to  know 


THE  PHENOMENON  OF  BLEEDING  7 

that  this  phenomenon  may  occur  in  individuals  who 
are  in  no  sense  bleeders,  haemophiliacs,  although  it  is 
possible  that  future  studies  may  place  them  in  that 
or  some  allied  category.  It  is  rarely  the  great  vessels 
that  cause  trouble  of  this  sort,  for  if  they  are  injured 
in  any  way  strenuous  efforts  are  made  immediately  to 
stop  the  flow.  The  hemorrhage  of  violence  is  usually 
of  such  nature  that  it  peremptorily  demands  imme- 
diate attention  and  secures  it. 

But  the  vast  majority  of  bleedings  make  no  such 
demands  and  as  a  consequence  frequently  go  unheeded. 
Who  ever  thinks  of  bothering  about  a  little  blood 
after  tooth  extraction?  yet  there  are  authentic  cases 
of  people  losing  their  lives  from  such  an  insignificant 
thing.  Quite  recently  it  was  necessary  for  me  to  work 
for  three  hours  to  control  bleeding  of  this  nature  that 
had  been  neglected  by  the  dentist  for  over  twenty-four 
hours,  the  patient  being  an  elderly  woman  who  had 
borne  eight  children  and  had  never  before  had  trouble 
of  a  similar  kind.  And  nose-bleeds — how  they  are 
neglected!  By  many  they  are  considered  evidences 
of  good  health !  Even  bleeding  following  nasal  oper- 
ations too  often  goes  unheeded.  About  two  years 
ago  I  saw  a  young  physician  who,  ten  days  following 
an  operation  on  his  sinuses,  had  had  a  hemorrhage  of 
such  severity  that  it  was  controlled  only  by  packing. 
In  forty-eight  hom*s  the  packs  were  removed  and  the 


8  BLOOD  TRANSFUSION 

patient  sent  home.  A  day  or  two  later  the  bleeding 
recurred,  and  the  nose  was  again  packed.  With  the 
knowledge  of  the  previous  hemorrhage  still  fresh  in 
mind,  the  surgeon  in  charge  might  have  exercised  more 
judgment  about  removing  his  packs,  but  he  was  so 
fearful  of  meningitis  from  the  damming  up  of  secre- 
tions consequent  upon  prolonged  tamponing,  that  he 
felt  it  unwise  to  leave  them  in.  He  had  handled  suc- 
cessfully so  many  similar  cases  of  bleeding  in  this 
manner  that  it  never  occurred  to  him  that  he  might  be 
dealing  with  something  just  a  bit  different  from  the 
common  variety.  Nor  could  he  be  con\'inced  that  this 
case  was  the  rule-proving  exception  until  his  patient 
had  become  so  frightfully  exsanguinated  by  repeated 
hemorrhages  that  his  life  was  only  saved  by  an  emer- 
gency transfusion,  and  by  nasal  packing  that  was  left 
in  situ  for  ten  days  before  being  finally  removed. 

To  have  uterine  bleedings  of  an  obscure,  stubborn, 
neglected  variety  is  a  common  occurrence.  There 
is  hardly  a  woman  who  at  some  time  during  her  life 
has  not  suffered  with  bleeding  of  an  abnormal  kind, 
different  from  her  usual  menstrual  flow.  In  many 
eases,  it  starts  spontaneously  and  ceases  spontaneously, 
probably  being  due  to  some  slight  abnormality  which 
rectifies  itself ;  while  occasionally  such  blood  loss  starts 
from  an  unrecognized  cause  but  fails  to  cease  without 
treatment.    Cases  are  even  on  record  where  complete 


THE  PHENOMENON  OF  BLEEDING  9 

removal  of  an  apparently  normal  uterus  was  necessi- 
tated by  continuous  unchecked  bleeding.  Sloughing 
fibroids  are  of  course  a  common  cause  and  the  meno- 
pause is  a  favorable  time  for  vicarious  bleeding  to  start 
up,  although  when  there  are  no  demonstrable  uterine 
abnormalities  it  is  hard  to  understand  the  bleeding.  In 
October,  1913, 1  was  asked  to  see  a  case  of  this  type,  in 
which  the  bleeding  had  progressed  so  far  that  the 
patient  was  too  weak  to  speak  above  a  whisper.  She 
had  failed  to  call  in  her  medical  adviser  until  the  flow 
had  been  going  on  for  weeks,  but  when  he  did  finally 
come  there  was  little  to  account  for  the  trouble,  and 
the  usual  forms  of  treatment  failed  to  give  relief.  A 
transfusion  of  blood  from  one  of  her  sons  caused  an 
immediate  cessation  of  the  bleeding,  and  a  prolonged 
but  uneventful  convalescence  ensued.  It  was  thought 
that  the  menopause  would  take  its  normal  course — she 
was  at  the  appropriate  age — but  for  three  years  there- 
after this  woman  menstruated  normally  and  was  in 
perfect  health.  At  the  end  of  that  time,  a  similar  in- 
tractable bleeding  set  in  for  the  relief  of  which  a  pan- 
hysterectomy was  performed  by  Dr.  W.  W.  Russell. 
The  specimen  revealed  a  carcinoma  of  the  body  of  the 
uterus. 

Gastric  and  intestinal  bleedings  are  practically 
always  the  result  of  some  ulcerative  process  that  in- 
volves vessels  of  larger  or  smaller  calibre,  as  the  case 


10  BLOOD  TRANSFUSION 

may  be.  They  may  be  difficult  to  locate  and  treat  but 
are  not  as  a  rule  difficult  to  understand,  except  that 
group  of  cases  coming  under  the  head  of  hemorrhagic 
diseases.  Some  of  these  latter  may  be  due  to  infection, 
possibly  all  are,  but,  if  so,  the  infectious  agency  has 
not  been  demonstrated.  They  seem  to  come  in  certain 
cases  from  developmental  errors  of  coagulation,  but 
whatever  their  source  the  condition  is  always  most 
dangerous.  Further  consideration  will  be  given  this 
subject  later  on. 

More  obscure  than  the  ordinary  intestinal  bleed- 
ings are  those  cases  of  bleeding  into  the  tissues  to 
which  the  group  name  of  purpura  is  given,  and  in 
which  the  blood  appears  literally  to  seep  through  the 
blood-vessel  walls.  Sahli  holds  that  this  phenomenon 
is  made  possible  by  an  inherent  developmental  defect 
in  the  makeup  of  the  vessel  wall,  but  according  to 
Duke  it  is  due  to  an  almost  total  lack  of  platelets  in 
the  blood.  In  mild  cases  only  the  subcutaneous  hemor- 
rhages are  seen  but  the  deeper  tissues  may  be  affected, 
and  in  certain  severe  cases  bleeding  into  the  internal 
organs  probably  occurs.  In  fact  it  is  in  this  way  that 
some  of  the  unaccountable  renal  hemorrhages  are  ex- 
plained. In  the  later  stages  of  purpura — and  in  the 
later  stages  of  all  the  hemorrhagic  group^  of  diseases 
— all  the  mucous  membranes  become  affected  and 
"  weep  "  a  thin  uncoagulable  blood.    In  November, 


THE  PHENOMENON  OF  BLEEDING  11 

1914,  I  transfused  such  a  case,  the  patient  being  a 
stalwart  young  farmer,  but  the  best  I  could  do  was  to 
secure  a  remission  of  a  few  months.  Following  the 
transfusion,  the  bleeding  ceased  and  a  marked  im- 
provement set  in,  but  the  inevitable  relapse  came 
along  a  few  months  later  and  the  patient  died. 

This  leads  us  to  a  consideration  of  that  remarkable 
condition  known  as  heemophilia,  recent  research  in 
which  seems  to  affirm  that  there  is  a  definite  abnor- 
mality in  the  blood  coagulatory  apparatus  of  those 
afflicted  with  the  condition.  A  theoretical  discussion 
of  the  matter  would  be  out  of  place  in  a  work  of  this 
practical  character,  but  a  clear  understanding  may 
perhaps  be  gained  by  a  brief  study  of  the  mechanism 
of  normal  blood  coagulation  according  to  the  prin- 
ciples of  Dr.  W.  H.  Howell,  of  the  Johns  Hopkins 
University,  who  has  probably  done  more  work  in  this 
field  than  any  other  investigator. 

Howell  believes  that  antithrombin,  present  in  small 
amounts  in  normal  blood  plasma,  binds  the  normally 
present  prothrombin  and  renders  it  inactive,  that  is, 
unable  to  start  clotting  of  the  blood.  But  whenever 
there  is  any  cell  injury  (tissue,  platelets,  blood-cells, 
etc.)  a  substance  called  thromboplastin  is  set  free 
which  immediately  neutralizes  the  antithrombin.  This 
frees  the  prothrombin,  which  is  thus  enabled  to  com- 
bine with  calcium  to  form  thrombin.    The  free  throm- 


12  BLOOD  TRANSFUSION 

bin  coagulates  the  fibrinogen,  giving  rise  to  the  normal 
clot.    His  theory  then  is  as  follows : 

Antithrombin  -< ( thromboplastin  ) 


Prothrombin 

\ 

(Thrombin) 

/  \ 

Calcium  (Clot) 

/ 

Fibrinogen. 

With  this  as  the  basis  of  his  studies,  Howell  first 
proved  that,  as  compared  to  normal  blood,  there  is  a 
most  marked  delay  in  the  spontaneous  coagulation  of 
the  hgemophilic  blood — ^and  that  "  the  deficient  coagu- 
lability was  due  to  some  permanent  alteration  in  the 
properties  of  the  blood."  These  deficiencies  resolved 
themselves  finally  into  an  actual  subnormal  amount 
of  prothrombin  in  the  circulating  blood  and,  since  anti- 
thrombin was  proved  to  be  present  in  normal  or 
slightly  supranormal  amounts,  Howell  concluded  that 
"  the  essential  condition  in  haemophilic  blood  which 
is  immediately  responsible  for  its  delayed  coagulation 
is  a  subnormal  amount  of  prothrombin  in  the  circu- 
lating blood."  He  therefore  says,  "  Hsemophiha  may 
be  defined  as  a  condition,  limited  to  the  male,  in  which 


THE  PHENOMENON  OF  BLEEDING  IS 

the  coagulation  time  of  the  blood  is  markedly  pro- 
longed in  consequence  of  a  deficiency  in  the  amount  of 
the  contained  prothrombin,  with  the  additional  char- 
acteristic that  the  defect  is  transmissible  by  heredity 
in  accordance  with  the  so-called  law  of  Nasse." 

This  is  not  only  a  scientific  but  a  satisfactory^  clini- 
cal definition  of  the  condition  as  well,  though  it  should 
be  understood,  in  addition,  that  there  may  be  sponta- 
neous cases  as  well  as  hereditary  ones.  Howell  him- 
self reports  one  such  instance  of  the  disease,  and  there 
are  others  on  record  in  which  careful  investigation 
fails  to  reveal  the  faintest  hereditary  cause;  there  are 
also  many  recorded  cases  of  the  so-called  "  bleeding 
tendency,"  that  is,  of  individuals  who  bleed  much  more 
freely  than  they  should,  and  longer,  and  on  slight 
provocation.  Perhaps  if  the  blood  of  these  people  were 
subjected  to  careful  investigation,  it  could  be  demon- 
strated that  they  are  either  true  haemophiliacs  or  of  a 
class  closely  allied.  Certain  it  is  that  there  are  many 
individuals  who,  while  not  actual  bleeders,  are  always 
worried  over  bleedings  that  ordinarily  cause  no  anxiety 
whatever,  and  they  are  justly  anxious,  since  it  is  always 
rather  trying  to  stop  their  bleeding,  and  as  a  result 
they  must  forego  the  comfort  and  convenience  of  many 
minor  operations.  Whether  these  imfortunates  ever 
actually  become  true  hsemophiliacs  or  not,  I  do  not 
know,  but  I  have  had  to  transfuse  a  patient  (the  doc- 


14  BLOOD  TRANSFUSION 

tor  mentioned  above)  who  was  known  to  possess  this 
bleeding  tendency  from  the  experience  of  two  opera- 
tions previous  to  the  one  in  which  hurried  transfusion 
was  all  that  could  arrest  an  exsanguinating  hemor- 
rhage. Oddly  enough,  he  has  subsequently  withstood 
an  operation  for  acute  appendicitis  without  difficulty. 

Still  other  forms  of  spontaneous  bleeding  are  occa- 
sionally encountered,  in  which  icterus  is  a  more  or  less 
predominant  feature.  Certain  forms,  according  to  the 
work  of  Whipple,  seem  to  fall  in  the  group  of  the  so- 
called  true  hemorrhagic  diseases,  but  the  majority  are 
caused  by  conditions  resulting  from  obstructive  types 
of  jaundice.  All  are  most  dangerous,  and  it  is  sad  to 
relate  that  the  therapy  is  unsatisfactory. 

Finally,  there  remain  for  consideration  those  cases 
of  anaemia  associated  with  actual  blood  disease,  such 
as  pernicious  anaemia,  the  leukaemias  and  the  anamia 
accompanying  malignant  disease.  These  invisible 
bleedings,  for  they  are  so,  usually  go  unnoticed  until 
the  host  is  weakened  to  such  extent  that  an  investi- 
gation as  to  cause  is  instituted.  Actual  bleeding  may 
never  take  place,  but  it  is  common  to  note  little  hemor- 
rhages from  the  mucous  membranes  late  in  the  course 
of  most  cases,  and  they  are  always  of  bad  prognostic 
significance.  Occasionally,  prompt  measm*es  may  stop 
them  for  a  while,  but  the  conditions  in  which  they  occur 
are  progressive,  and  recurrence  is  the  rule.    Toward 


THE  PHENOMENON  OF  BLEEDING  15 

the  end,  it  is  not  uncommon  to  find  every  mucous 
membrane  "  weeping  "  the  thin  uncoagulable  blood 
that  portends  dissolution.  A  more  detailed  consider- 
ation will  be  given  this  topic  later  on. 

The  above  introductory  surv^ey  makes  it  evident 
that  blood  may  be  lost  in  many  different  ways  and 
from  a  host  of  causes,  some  of  which  are  understood, 
while  others  are  still  obscure ;  that  even  the  most  insig- 
nificant bleeding  may  resolve  itself  into  a  hemori'hage 
of  most  alarming  character,  and  that,  with  this  knowl- 
edge, there  is  little  excuse  for  the  prevalent  indiffer- 
ence to  blood  loss  of  the  minor  grades.  The  successful 
study  of  hemorrhage,  and  hemorrhagic  conditions,  de- 
pends upon  a  broad  conception  of  the  many  factors 
involved  in  causation  and  control,  to  which  an  under- 
standing both  of  general  medicine  and  surgery  is 
indispensable. 

REFERENCES 

JBernheim,  B.  M. :  "  The  Relation  of  the  Blood-vessel  Wall  to 
Coagulation  of  the  Blood."  J.  A.  M.  A„  July  25,  1910, 
vol.  Iv. 

Howell,  W.  H.:  "A  Text-Book  of  Physiology."  W.  B. 
Saunders  Company,  Philadelphia,  1915. 

Howell,  W.  H.:  "The  Condition  of  the  Blood  in  Haemo- 
philia, Thrombosis  and  Purpura."  Archives  of  Internal 
Medicine,  January,  1914,  vol.  xiii. 

Morawitz,  P. :  "  Blut  and  Blutkrankheiten."  Handb,  d.  inn. 


16  BLOOD  TRANSFUSION 

Med,  (Mohr  and  Staehlin),  Berlin,  1912,  w.  92-346,  2  pi. 

Simon,  C.  E. :  "A  Manual  of  Clinical  Diagnosis."  Lea  and 
Febiger,  Philadelphia,  1914. 

Lee,  Roger  I.,  and  Vincent,  Beth:  "The  Coagulation  of 
Normal  Human  Blood."  Arch,  of  Int.  Med.,  March, 
1914,  vol.  xiii,  pp.  398-425. 

Whipple,  G.  W. :  "  II  Hemorrhagic  Disease.  Antithrombin 
and  Prothrombin  Factors."  Arch,  of  Int.  Med.,  Decem- 
ber, 1913,  vol.  xii,  pp.  637-699. 


CHAPTER  ir 

DIAGNOSIS  OF  HEMORRHAGE 

DIFFERENTIAJL  DIAGNOSIS  BETWEEN  CONCEALED  HEM- 
OERHAGE,  SHOCK,  GENERAL  PERITONITIS,  HEART 
COLLAPSE,  PERFORATED  GASTRIC  ULCER  AND  ACUTE 
PANCREATITIS 

Loss  of  blood  in  any  considerable  quantity  is 
accompanied  by  a  sequence  of  signs  and  symptoms 
which  ^re  of  such  character  as  to  be  unmistakable  in 
the  majority  of  instances,  but  which  are,  unfortu- 
nately, not  classically  characteristic  of  hemorrhage 
alone.  ^  So  that,  where  there  is  no  visible  evidence  of 
bleeding  and  conditions  are  such  that,  although  hemor- 
rhage is  strongly  suspected,  any  one  of  a  number  of 
other  causes  may  be  responsible  for  the  trouble,  a 
proper  diagnosis  can  only  be  reached  by  a  judicial 
consideration  of  all  those  maladies  which  might  give 
rise  to  the  signs  and  symptoms  encountered. 

To  take  up  the  matter  basically,  of  first  impor- 
tance is  an  accurate  past  history,  a  thing  sometimes 
very  difficult  to  secure.  The  patient  may  be  reticent 
because  of  a  desire  to  conceal  an  indiscretion — as  in  the 
case  of  an  unmarried  woman  suspected  of  having  a 
ruptured  ectopic  pregnancy — sometimes  the  doctor  is 

2  17 


18  BLOOD  TRANSFUSION 

careless  in  his  questioning,  but  more  often  the  anxiety 
of  the  patient  and  relatives  is  so  intense  that  important 
details  of  the  past  history  are  actually  forgotten.  In 
general,  though,  a  ti-ue  detailed  statement  can  be  had 
with  care  and  patience,  and  one  has  only  to  look  back 
over  one's  obscure  cases  to  realize  how  clear  some  of 
them  might  have  been  had  a  little  more  care  been 
exercised  in  obtaining  an  accurate  history. 

'Next  in  importance  to  the  previous  history  is  the 
method  of  onset  and,  in  sequence,  the  course  of  progres- 
sion of  the  illness  until  finally  the  time  comes  for  an 
intensive  study  of  all  features  of  the  case  in  hand,  in- 
cluding actual  physical  examination  of  the  patient  and 
laboratory  tests  of  every  available  kind.  Wliere  haste 
is  necessary  (and  time  is  an  important  element)  certain 
steps  in  the  examination  must  be  eliminated,  but  to 
slur  over  laboratory  tests  because  they  are  thought  to 
have  no  bearing  on  the  case  is  as  reprehensible  as  is 
failure  to  inquire  into  the  past  history.  Frequently 
it  is  the  imexpected  that  happens  and  light  is  shed 
from  a  surprising  quarter. 

A  cold  clammy  skin,  a  pulse  of  little  force  and  less 
volimie,  but  extreme  rapidity  and  a  little  irregularity, 
a  breathing  hardly  perceptible  but  rapid,  a  pinched 
expression,  facies  cadaverously  cyanotic,  a  blood-pres- 
sure steadily  falling  and  a  patient  in  profound  pros- 
tration— hemorrhage  ?    Possibly.    These  are  the  usual 


DIAGNOSIS  OF  HEMORRHAGE  19 

signs  certainly,  but  they  are  usual  for  conditions  other 
than  hemorrhage  as  well.  And  if  there  is  air-hunger, 
with  sighing  attempts  to  get  air,  instead  of  the  shallpw 
rapid  breathing,  and  an  increasing  restlessness — 
hemorrhage?  Almost  certainly,  but  not  necessarily. 
Broken  compensation  in  an  old  cardiac  case  quite  com- 
monly is  accompanied  by  air-hunger  and  restlessness, 
but  a  careful  history  might  rule  out  this  condition  even 
if  an  examination  should  fail  to  do  so — yet  once  in  a 
great  while  neither  of  them  will.  But  what  about  the 
blood  findings?  In  general  they  are  of  little  imme- 
diate aid,  because  the  compensatory  tightening  up  of 
the  vascular  apparatus,  even  in  cases  of  severe  bleed- 
ings, is  such  that  great  drops  in  hamoglobin  and  red 
cell  counts  are  unusual  until  many  hours  after  the 
trouble  has  begun,  and  since  the  normal  for  the  indi- 
vidual is  generally  unknown,  any  fall  except  a  great 
one  is  of  little  immediate  diagnostic  aid.  The  esti- 
mations, though,  should  always  be  made,  because  every 
once  in  a  while  an  unmistakable  drop  does  occur  and 
the  case  is  clear.  Besides,  the  leucocyte  count  might 
prove  illuminating,  especially  in  the  obscure  abdomi- 
nal conditions. 

Where  the  history  would  seem  to  indicate  the  pos- 
sibility of  hemorrhage,  or  where  there  is  a  known  cause 
of  bleeding,  such  as  operation  or  an  injury,  the  signs 
and  symptoms  enumerated  in  the  previous  paragraph 


20  BLOOD  TRANSFUSION 

are  considered  classical,  and  a  diagnosis  of  hemorrhage 
would  be  justified.  One  may  go  even  further  and  say 
that  in  the  absence  of  some  of  them,  there  are  cer- 
tain types  of  hemorrhage  whose  mode  of  onset  is  so 
typical  that  a  diagnosis  other  than  hemorrhage  is 
ftlmost  inconceivable,  although  the  possibility  of  error 
cannot  be  entirely  overlooked.  I  refer  particularly  to 
those  instances  of  ruptured  ectopic  pregnancy,  where 
a  woman  previously  well,  in  the  child-bearing  period, 
has  a  sudden  sharp  pain  in  her  abdomen,  faints,  and 
on  reviving,  is  prostrated.  Hemon-'bage  is  written  all 
over  her  features.  And  the  typhoid  patient  who  suf- 
fers a  sudden  severe  intestinal  hemorrhage  occasionally 
presents  the  same  picture. 

But  what  about  those  cases  where  other  possi- 
bilities and  probabilities  come  up  for  consideration? 
The  post-operative  cases  that  fail  to  react,  or,  reacting, 
slip  away  again;  the  sudden  collapse  of  individuals, 
previously  well,  whose  history  is  either  negative  or  but 
faintly  suggestive;  the  typhoid  patient  whose  sinking 
spell  may  be  due  to  perforation  as  well  as  hemorrhage, 
or  to  both,  or  to  neither;  the  individual  injured  but 
evincing  no  evidence  of  his  injury  other  than  profound 
prostration?  Where  are  our  classical  signs?  They 
may  be  present  in  part,  or  in  toto,  and  they  may  be 
just  as  eloquent  as  ever  in  proclaiming  trouble  of  a 
serious  nature,  but  no  longer  are  they  classical  for 


DIAGNOSIS  OF  HEMORRHAGE  21 

hemorrhage.  These  are  the  moments  when  a  calm 
judicial  mind  is  greatly  to  be  desired. 

If  I  were  asked  what  one  specific  discovery  would 
do  the  most  good  to  the  greatest  number  in  surgery, 
I  would  almost  unhesitatingly  reply,  "A  pocket  flash- 
lamp  of  such  power  that  the  inner  workings  of  the 
human  abdomen  could  be  distinguished  " — for  it  is 
the  abdomen  above  all  else  that  mystifies,  and  until  the 
time  comes  when  we  shall  actually  be  able  to  see  what 
is  going  on,  it  will  continue  to  do  so.  But  we  have 
no  magic  lamp,  and  the  differential  diagnosis  of  intra- 
abdominal conditions  is  at  present  so  intricate  and 
unsatisfactory  and  often  based  on  evidence  of  such 
flimsy  nature,  that  it  really  amounts  to  little  more 
than  a  guess.  Fortunately,  however,  intuition  plays 
its  part  and  the  man  who  is  more  widely  experienced, 
who  is  perhaps  better  seasoned  by  advancing  years 
than  his  colleagues,  and  more  used  to  reasoning  things 
out,  comes  to  have  a  sort  of  sixth  sense  that  guides 
him  to  an  interpretation  more  nearly  correct  than 
others  reach — for  certainly  the  signs  and  symptoms 
are  apparent  to  all  and  are  pathognomonic  no  more 
for  him  than  for  others. 

I  was  once  asked  to  see  a  woman,  who  had  under- 
gone a  resection  of  part  of  her  sigmoid,  for  a  new 
growth,  a  lateral  anastomosis  being  the  means  of  unit- 
ing the  severed  bowel.    The  operation  had  been  done 


22  BLOOD  TRANSFUSION 

about  eighteen  hours  before  by  Dr.  John  M.  T. 
Finney  in  his  characteristically  thorough  manner,  and 
the  woman  had  left  the  table  in  good  condition  and  had 
continued  to  do  well  for  twelve  hours  when,  most  un- 
expectedly, she  had  an  alarming  sinking  spell  during 
which  she  almost  died.  Her  pulse  became  extremely 
rapid,  breathing  very  difficult,  and  it  looked  very  much 
as  if  there  had  been  a  temporary  heart  collapse  for 
which  the  usual  restoratives  were  promptly  admin- 
istered. They  gave  but  little  relief,  however,  and,  as 
the  patient's  condition  seemed  desperate,  a  salt  infu- 
sion was  at  once  started,  under  the  assumption  that 
an  intra-abdominal  hemorrhage  was  in  progress.  This 
helped  matters  a  little  only,  and  still  no  signs  of  bleed- 
ing could  be  detected;  drains  had  been  placed  through 
a  puncture  wound,  but  no  blood  showed  on  the  dress- 
ings and  their  removal  revealed  none  along  the  drain- 
age tract  nor  within  that  area  of  the  abdomen  which 
could  be  investigated. 

When  I  saw  her  the  picture  was  certainly  one  of 
profound  hemorrhage  and  shock.  There  were  the 
rapid  respiration,  the  rapid  thready  pulse,  the  pinched 
expression,  the  very  low  blood-pressure,  and  the  cold 
clammy  skin.  The  abdomen  was  soft.  Blood  counts 
were  non-committal,  as  usually  happens  when  they 
are  most  needed.  But  since  no  evidence  of  bleeding 
could  be  found  in  spite  of  repeated  search,  and  the 


DIAGNOSIS  OF  HEMORRHAGE  23 

woman  was  in  the  advanced  fifties,  I  rather  inclined 
to  the  diagnosis  of  broken  heart  compensation  and 
advised  against  transfusion,  for  wliich  I  was  con- 
sulted. Dr.  Finney  was  at  a  loss  for  a  diagnosis  as 
were  all  others  concerned,  including  one  of  the  best 
medical  consultants  in  the  city.  Thus  matters  hung 
for  eight  hours  longer,  during  which  time  everything 
conceivable  was  done  to  revive  the  patient — all  im- 
availing.  At  the  end  of  this  period  the  woman's 
condition  was  so  critical  that,  under  the  assumption 
that  an  intra-abdominal  catastrophe  of  some  nature 
surely  had  occurred  and  was  responsible  for  the 
trouble,  it  was  decided  to  reopen  the  abdomen  and 
look  in,  a  preliminary  transfusion  being  done  in  order 
to  prepare  the  way.  With  the  introduction  of  the 
first  100  c.c.  of  blood  from  her  son,  a  slight  improve- 
ment took  place,  but  as  further  improvement  failed  to 
follow  the  second  100  c.c,  the  transfusion  was  tem- 
porarily stopped.  Dr.  Finney  was  just  preparing  to 
open  the  wound  when  the  patient  died.  I  thereupon 
opened  it  myself  and  discovered  no  blood  at  all,  but 
a  rather  small  amount  of  serosanguineous,  thin  fluid 
which  under  the  miscroscope  contained  myriads  of 
streptococci!  And  a  streptococcus  peritonitis  had 
never  occurred  to  one  of  us.  Could  anything  be 
more  baffling?  An  intra-abdominal  catastrophe  had 
truly  occurred!    There  had  been  no  cases  of  strep  to- 


24  BLOOD  TRANSFUSION 

coccus  infection  of  any  kind  in  the  hospital  for  months 
and  no  cases  of  streptococcus  peritonitis  for  over  a 
year,  and  in  these  days  of  aseptic  surgery  a  fulminat- 
ing streptococcus  peritonitis  is  an  extremely  rare 
occurrence.  Here  we  had  every  conceivable  sign  and 
symptom  of  hemorrhage,  of  what  is  so  glibly  termed 
shock,  and  of  heart  collapse,  and  still  not  one  of  them 
was  the  underlying  cause.  The  patient  was  pro- 
foundly shocked,  it  is  true,  but  this  was  but  the  ex- 
pression of  the  obscure  cause.  I  confess  that  I  was 
imaware  prior  to  this  that  a  streptococcus  peritonitis 
could  simulate  these  conditions.  Since  then  I  have 
seen  one  other  similar  case,  also  post-operative,  and 
for  which  I  was  summoned  to  do  a  transfusion  for 
bleeding.  I  diagnosed  this  one  correctly.  The  patient 
died  four  hours  later,  twenty-four  hours  after  the 
operation,  and  my  diagnosis  was  confirmed.  Differ- 
ential diagnosis  is  extremely  difficult  and  experience 
is  a  great  asset. 

I  mention  heart  collapse  as  a  possible  obscuring 
element  in  the  interpretation  of  seeming  hemorrhage 
because  of  another  most  instructive  mistake  made  two 
years  ago.  Ordinarily  a  sudden  break  in  heart  com- 
pensation is  recognized  by  an  alert  physician  without 
great  difficulty,  and  the  diagnosis  of  hemorrhage  is 
rarely  complicated  by  the  suggestion  of  this  as  a  possi- 
bility, but  late  one  night  I  was  hurriedly  called  to  the 


DIAGNOSIS  OF  HEMORRHAGE  25 

hospital  to  see  what  was  considered  an  alarming  case 
of  concealed  intestinal  bleeding  in  a  young  woman  who 
had  been  rmming  an  ordinary  typhoid  course.  While 
using  the  bed  pan,  the  patient  had  suddenly  suffered 
a  most  alarming  collapse,  the  chief  manifestations 
being  loss  of  consciousness,  extreme  pallor,  rapid  pulse 
and  apparent  shortness  of  breath.  Prompt  restora- 
tive measures  were  instituted  with  some  success,  but 
the  condition  remained  quite  alarming  and,  all  things 
considered,  a  diagnosis  of  concealed  typhoid  hemor- 
rhage seemed  proper.  The  haemoglobin  and  red  counts 
were  made,  but  as  usual  could  not  be  relied  upon  as 
true  indicators.  A  more  reliable  index  of  probable 
bleeding  seemed  to  be  the  blood-pressure,  which  was 
only  90  mm. 

Before  I  arrived,  strophanthin  had  been  given  and 
an  infusion  of  700  c.c.  of  salt  solution  which  had  been 
taken  up  with  slight,  but  not  marked,  improvement. 
There  had  also  been  a  consultation  between  the 
patient's  physician,  a  man  instructed  in  all  branches 
of  medicine,  and  one  of  the  leading  consultants  of  the 
city,  both  of  whom  had  gone  over  the  situation  in  their 
usual  painstaking  manner,  and  had  ruled  out  heart 
collapse  in  favor  of  hemorrhage. 

To  me  the  picture  was  typical,  so  I  warned  against 
fm-ther  infusions,  fearing  that  renewed  or  prolonged 
bleeding  might  be  encouraged  by  filling  up  the  vessels. 


26  BLOOD  TRANSFUSION 

But  it  did  not  seem  to  any  of  us  that  the  patient  was 
in  imminent  danger;  to  be  sure  a  blood-pressure  of 
90  mm.  is  near  the  danger  line,  but  a  low  pressure  and 
a  slowed  circulation  is  to  be  desired  in  cases  of  obscure 
intestinal  bleeding.  We  decided  to  watch  the  patient 
most  carefully  for  evidences  of  further  bleeding,  mean- 
time preparing  for  transfusion  by  having  the  tests 
made  for  prospective  donors. 

By  morning  the  patient  was  slightly  improved; 
the  pulse  was  a  bit  slower  and  the  blood-pressure  about 
the  same.  We  waited,  and  by  evening  we  decided  to 
wait  still  longer.  We  are  still  waiting  to  see  the 
slightest  evidence  of  any  bleeding.  There  were  no 
further  disturbances,  and  the  patient  ran  the  typical 
typhoid  course  from  which  she  made  an  uninterrupted 
recovery. 

Looking  backward,  it  seems  that  the  lack  of  any 
marked  abdominal  distress  or  muscular  rigidity  might 
have  put  us  on  our  guard,  but  abdominal  hemorrhage 
is  not  always  accompanied  by  marked  physical  signs. 
Then,  too,  it  hardly  seems  likely  that  an  embarrassed 
circulation  could  take  up  with  apparent  avidity  700 
C.C.  of  salt  solution  without  becoming  still  further  em- 
barrassed, and  this  did  not  happen — possibly  as  a  result 
of  the  supportive  strophanthin.  We  considered,  at  the 
time,  the  possibility  of  an  ulcer  having  perforated  with 
the  resultant  peritonitis  and  shock  and  possible  intra- 


DL\GNOSIS  OF  HEMORRHAGE  27 

peritoneal  bleeding,  but  the  abdominal  examination 
appeared  to  eliminate  this  and  no  sign  or  symptom 
of  peritonitis  appeared  subsequently ;  so  we  are  forced 
to  the  conclusion  that  we  were  dealing  with  a  pure  case 
of  heart  collapse  that  so  nearly  approximated  a  con- 
cealed intestinal  hemorrhage  as  to  render  differential 
diagnosis  impossible. 

We  do  not  know  exactly  what  shock  is;  in  fact, 
we  have  no  standard  conception  of  it  other  than  that 
it  is  a  condition  of  lowered  vitality,  the  index  of  which 
is  a  semiconsciousness,  a  relaxation  of  practically  all 
the  organic  faculties,  and  a  blood-pressure  of  minimal 
limits,  to  say  the  least.  Such  a  state  could  hardly 
come  about  except  through  an  accident  of  violence  or 
as  an  accompaniment  or  result  of  some  other  condition, 
such  as  hemorrhage,  perforated  ulcer,  et  cetera,  so 
that  pure  shock  as  such  rarely  has  to  be  eliminated — 
with  perhaps  one  exception,  namely,  following  a  dan- 
gerous and  prolonged  operation.  Loss  of  blood  dur- 
ing operation,  peritoneal  irritation  or  manhandling, 
violence  in  reducing  fractures,  prolonged,  carelessly 
given  anaesthesia,  all  these  factors  not  infrequently 
prove  too  much  of  a  bm-den,  and  the  so-called  post- 
operative reaction  and  return  to  consciousness  is  de- 
layed or  fails  to  occur — or  the  reaction  and  conscious- 
ness may  appear  only  to  be  accompanied  or  followed 
bj^  a  lassitude  which  progresses,  in  spite  of  proper 


28  BLOOD  TRANSFUSION 

treatment,  to  an  alarming  collapse.     Is  this  hemor- 
rhage? shock?  or  both? 

The  type  of  operation,  the  operative  methods  in- 
volved, the  whole  operative  program  studied  from 
every  angle  will  occasionally  give  the  clue  to  the 
trouble,  although  I  am  rather  of  the  impression  that 
nowadays,  almost  all  surgeons  are  quite  careful  of 
their  hasmostasis  for  the  simple  reason  that  they  have 
gotten  into  difficulty  at  some  previous  time  as  a  result 
of  carelessness  or  have  seen  the  consequences  of  it  in 
others.  Still  there  are  many  quite  remiss  in  those 
little  refinements,  such  as  deftness,  recognition  of 
rights  of  tissues,  et  cetera,  which  go  to  make  the 
finished  operator.  However,  the  surgeon's  skill  taken 
for  granted,  I  should  incline  toward  a  diagnosis  of 
shock  rather  than  post-operative  hemorrhage,  unless 
the  bleeding  can  be  demonstrated,  or  there  has  been 
some  definite  reason  to  suspect  it.  Delayed  return  to 
consciousness  is  not  uncommon  after  operation  and 
certain  individuals  seem  more  sensitive  to  mechanical 
manipulations  than  others,  factors  to  be  borne  in  mind. 
The  safest  way  to  estimate  these  patients  is  to  sit  by 
the  bedside  and  study  every  feature  connected  with 
the  case  over  a  considerable  period  of  time,  taking 
blood-pressure  readings  at  frequent  intervals  and 
making  blood  counts  at  definite  periods  of  every  half 
hour.    A  persistently  diminishing  blood-pressure  and 


DIAGNOSIS  OF  HEMORRHAGE  29 

decreasing  blood  count,  with  no  improvement  in  symp- 
toms in  spite  of  proper  treatment,  would  indicate 
hemorrhage  or  at  least  warrant  an  investigation  of  the 
operative  field. 

An  acute  pancreatitis  is  usually  accompanied  by 
a  state  of  such  profound  collapse  and  such  rigid  ab- 
dominal walls  that  hemon-hage  is  hardly  to  be  con- 
sidered, and  a  perforated  gastric  ulcer  belongs  in  the 
same  category,  in  addition  to  having  a  history  which, 
if  obtainable,  is  usually  sufficient  to  point  the  way  to 
the  probable  diagnosis.  Both  conditions  demand,  and 
usually  receive,  immediate  operation,  with  the  clarify- 
ing of  any  diagnostic  doubt.  I  mention  them  in  this 
connection  because  they  must  be  kept  in  mind  in  any 
consideration  involving  the  abdomen,  but  I  have  never 
had  occasion  to  do  a  transfusion  in  the  initial  state 
of  either  condition.  It  is  conceivable,  of  course,  that 
a  good  sized  vessel  may  be  eroded  at  the  site  of  per- 
foration— indeed,  cases  are  on  record  where  this  has 
happened — but  as  a  rule  this  does  not  occur.  Further- 
more, it  is  also  true  that  the  vast  majority  of  those 
gastric  ulcers  that  do  bleed  do  not  perforate — at  least 
not  at  the  time  of  the  hemorrhage.  The  possibility 
of  this  condition  and  that  of  acute  pancreatitis  is  merely 
to  be  borne  in  mind  as  a  possible  eventuality  where 
there  are  strong  grounds  for  suspecting  hemorrhage. 

The  blood  findings  in  oases  of  acute  hemorrhage 


80  BLOOD  TRANSFUSION 

are  peculiar  to  say  the  least.  The  red  cells  are  sup- 
posed to  fall  in  number,  the  haemoglobin  is  also  ex- 
pected to  fall,  while  the  white  cell  count  is  supposed 
to  rise;  as  a  matter  of  fact,  they  do  act  as  scheduled 
in  many  cases,  but  the  instances  in  which  they  do  not 
are  so  frequent,  that  unless  serial  readings  are  taken 
little  dependence  is  to  be  placed  on  them.  In  1909 
Crile  reported  eighteen  observations  on  the  haemo- 
globin and  red  cell  changes  in  donors  after  transfu- 
sion. There  was  a  fall  in  the  red  cells  seventeen  times 
out  of  the  eighteen,  but  in  five  instances  the  fall  was 
very  slight,  while  the  hajmoglobin  fell  twelve  times  and 
remained  unchanged  six  times.  Of  thirteen  observa- 
tions on  the  white  cells,  there  was  a  rise  in  twelve,  but 
it  was  slight  in  two  of  them,  while  in  one  case  there  was 
a  fall.  Several  of  the  cases  in  which  no  fall  could  be 
detected,  or  in  which  it  was  very  slight  at  first,  showed 
distinct  falls,  some  large,  some  small,  a  number  of 
hours  (seven,  eight,  or  ten)  after  transfusion.  And 
curiously  enough  the  red  cells  and  haemoglobin  do  not 
necessarily  correspond  in  their  fall.  In  certain  cases 
a  definite  decrease  in  the  reds  was  noted,  but  the 
ha2moglobin  decrease  was  so  slight  as  to  be  of  no 
significance. 

It  is  therefore  evident — for  Crile's  observations 
have  been  confirmed  by  everyone  who  has  investi- 
gated the  matter — that  single  blood  examinations  in 


DIAGNOSIS  OF  HEMORRHAGE  31 

cases  of  severe  hemorrhage  cannot  be  taken  too  seri- 
ously. In  the  first  place,  the  normal  blood  count 
varies  within  fairly  wide  limits  with  each  individual, 
and  it  is  extremely  rare  that  the  normal  is  known  for 
the  patient  under  consideration.  When  we  add  to 
this  the  fact  that  it  is  always  extremely  difficult  to 
judge  as  to  the  amount  of  blood  lost,  one  can  readily 
see  that  the  difficulties  in  this  direction  are  practically 
insurmountable.  Nor  is  it  hard  to  understand  why  ex- 
cessive blood  losses  need  not  necessarily  be  indicated 
by  estimations  made  during  or  shortly  after  the  hemor- 
rhage, since  it  is  well  known  that  as  blood  flows  out 
of  its  containing  vessels,  a  compensatory  involuntaiy 
contraction  of  the  vessels  takes  place  with  a  general 
narrowing  of  their  lumen,  thus  giving  more  or  less 
stability  to  the  blood-pressure.  The  unshed  blood 
remains  undiluted  in  the  contracted  vessels  and  counts 
made  during  this  period  are  consequently  practically 
without  value  so  far  as  revealing  the  true  state  of 
affairs  is  concerned.  Not  until  the  compensatory  con- 
traction of  the  vessels  relaxes,  can  the  surromiding 
tissue  plasma  pour  into  them,  and  as  this  usually  does 
not  take  place  till  some  hours  after  the  hemorrhage, 
there  is  actually  little  or  no  blood  dilution.  It  is  true 
that  there  has  been  less  blood  all  along,  but  there  also 
has  been  less  blood-vessel  lumen,  less  actual  space  to 
be  filled.    When  the  relaxation  does  occur  more  space 


82  BLOOD  TRANSFUSION 

needs  to  be  filled,  for  which  the  actual  blood  is  insuiR- 
cient,  so  plasma  is  drawn  in  from  the  surrounding 
tissues  to  make  up  the  bulk,  and  as  plasma  contains 
no  cells,  a  count  made  at  this  time  will  show  true 
depletion. 

The  differential  diagnosis,  then,  between  hemor- 
rhage and  conditions  that  simulate  it,  is  a  most  delicate 
matter  in  many  eases.  Personally,  I  have  never  seen 
an  out-and-out  case  of  severe  bleeding  which  had  a 
high  leucocytosis,  so  that  I  am  accustomed  to  incline 
toward  a  condition  other  than  hemorrhage,  when  this 
feature  is  found.  At  the  same  time,  it  has  been  unusual 
to  encounter  a  leucocytosis  sufficiently  high  to  abso- 
lutely rule  out  hemorrhage  in  many  of  the  obscure 
cases  that  have  come  under  my  observation  for  differ- 
entiation. Once  in  a  while  it  is  there,  but  not  in  the 
profound  pulseless  cases,  as  a  rule. 

I  can  only  conclude  this  chapter  with  the  reiterated 
advice  to  take  a  most  careful  history  and  to  leave  no 
test,  laboratory  or  other  kind,  undone,  and  the  sug- 
gestion that  the  countenances  of  patients  who  have 
suffered  blood  loss  be  studied.  They  come  to  have 
a  look  which,  though  not  actually  characteristic- 
ally diagnostic,  is  different  from  the  appearance  pre- 
sented by  those  whose  condition  is  the  result  of  some- 
thing other  than  bleeding,  a  look  truly  gruesome  and 
which  I  can  best  describe  as  cadaverously  cyanotic. 


DIAGNOSIS  OF  HEMORRHAGE  38 

REFERENCES 

Barker,  L.  F. :  "  Monographic  Medicine,"  vol.  iii,  Appleton, 
1916. 

Crile,  G.  W. :  "  Hemorrhage  and  Transfusion."  Appleton 
and  Company,  N.  Y.,  1909. 

Hirschfelder,  A.  D. :  "  Diseases  of  the  Heart  and  Aorta." 
J.  B.  Lippincott  Company,  Philadelphia,  1910. 

Janevray,  H.  H.,  and  Ewing,  E.  M. :  "  The  Nature  of  Shock." 
Annals  of  Surgery,  February,  1914. 

Mayo,  Wm.  J. :  "  Hemorrhage  from  the  Stomach  and  Duo- 
denum." Surgery,  Gynecology  and  Obstetrics,  May, 
1908,  pp.  451-454. 

Osier,  W. :  "  Practice  of  Medicine."  Appleton,  8th  ed.,  1912. 

Osier  and  McCrae :  "  Modem  Medicine,"  second  edition,  Phila- 
delphia, 1915. 

Thompson,  J.  E. :  "  Remarks  on  Fatal  Hemorrhage  from 
Erosion  of  the  Gastroduodenal  Artery  by  Duodenal 
Ulcers."  Annals  of  Surgery,  May,  1913. 


CHAPTER  III 

CONTROL  OF  HEMORRHAGE.  FACTORS  INVOLVED 

IN  A  DETERMINATION  OF  DANGER  LIMITS. 

BLOOD-PRESSURE 

The  control  of  bleeding,  in  general,  is  so  well 
known  and  the  means  at  our  disposal  for  accomplish- 
ing this  purpose  are  so  uniformly  used  that  detailed 
consideration  need  hardly  be  given  each  individual 
form.  Pressure,  the  suture  of  lacerated  tissues,  the 
ligation  of  great  vessels  and  the  pack,  are  common 
elementary  measures  for  attacking  visible  hemorrhages 
or  those  amenable  to  operative  interference.  But  in- 
stances frequently  arise  where  a  successful  outcome 
depends  less  upon  actual  mechanical  measures  than 
upon  a  keen  judgment  as  to  the  time  or  the  form  of 
their  application,  less  upon  the  actual  cessation  of 
bleeding  than  upon  a  prevention  of  its  ever  starting, 
and,  finally,  upon  a  coordination  of  efforts  that  in- 
volves, on  the  one  hand,  the  most  painstaking  investi- 
gations as  to  cause  and,  on  the  other,  a  broad  com- 
prehension of  the  many  factors  concerned  with  blood 
loss  and  blood  coagulation. 

The  intensive  study  of  hemorrhage  has  really  been 
neglected  up  to  the  present  time  and  for  the  very 
good  reason  that  no  special  purpose  could  have  been 

84 


CONTROL  OF  HEMORRHAGE  35 

served  by  a  deeper  knowledge  of  its  workings.  Until 
the  advent  of  blood  transfusion  in  a  practical  form, 
there  was  no  dependable  reserve  remedy  in  the  phy- 
sician's armamentarimn  so  far  as  great  blood  losses 
were  concerned  and  many  features  connected  with 
the  phenomenon  of  bleeding  stand  out  in  the  high 
light  of  present-day  knowledge  that  were  quite  ob- 
scure not  very  long  ago.  Chief  among  these  is  the 
amazing  futility  of  drugs  and  next  in  order  is  the 
abuse  of  salt  solution. 

One  has  only  to  consult  the  hospital  records  of  a 
few  years  ago  to  discover  how  profoundly  drugged 
were  most  patients  who  had  the  misfortune  to  bleed, 
and  a  little  closer  study  of  the  same  records  will  show 
how  thoroughly  water-logged  by  salt  solution  they 
were,  in  addition.  That  any  truly  serious  hemorrhages 
were  successfully  combated  is  a  wonder,  and  that  more 
fatalities  did  not  occur  speaks  rather  for  nature's  re- 
cuperative powers  than  for  the  medical  man's  skill  and 
comprehension.  The  custom  of  drug  therapy  un- 
doubtedly arose  from  a  feeling  of  hopelessness  in  the 
face  of  intractable  bleeding  and  the  necessity  of  doing 
something  in  a  losing  fight,  while  the  salt  solution 
therapy  was  a  later  development  consequent  upon  the 
discovery  that  many  individuals  whose  bleeding  had 
been  stopped  before  it  progressed  too  far  could  be 
saved  by  this  means.    That  it  had  its  limits  and  was 


86  BLOOD  TRANSFUSION 

capable  of  doing  great  harm  did  not  become  apparent 
till  rather  recently. 

Morphine  judiciously  administered  is  of  distinct 
benefit  in  quieting  a  restless  patient  and  in  stilling 
active  peristalsis  where  intestinal  bleeding  is  in  process, 
but  its  indiscriminate  or  continued  use  is  to  be  avoided, 
because,  in  the  first  place,  a  false  security  may  be 
brought  about,  and,  in  the  second  place,  the  large  or 
cumulative  doses  tend  to  lower  the  blood-pressure,  a 
distinct  harm  oftentimes  because  the  bleeding  itself 
brings  this  about,  and  minimal  limits  are  dangerous 
and  undesirable.  Stimulants  like  strychnine,  cam- 
phorated oil,  atropin,  digitalis,  strophanthin  may 
possibly  steady  a  faltering  heart,  but  it  is  well  to 
remember  that  the  heart  is  not  the  cause  of  the  bleed- 
ing, and  any  irregularity  is  liable  to  be  due  to  causes 
other  than  the  heart  itself. 

Ergot  and  pituitrin  doubtless  have  their  places  in 
ordinary  obstetrics,  but  once  a  uterus  has  become 
atonic  to  such  extent  that  bleeding  has  become  serious 
enough  to  require  packing,  I  have  rarely  seen  either 
of  them  be  of  further  service,  although  I  have  seen  re- 
peated injections  of  one  or  both  given.  It  may  be  that 
the  atonic  condition  came  about  because  they  failed 
to  do  their  work  in  the  first  and  usual  instance.  That 
we  have  no  means  of  ascertaining,  but  certain  it  is  that 
later  on  they  do  not  seem  to  help  matters. 


CONTROL  OF  HEMORRHAGE  37 

In  the  same  category  may  be  placed  the  various 
sera.  Cases  are  on  record  where  rabbit  serum  has 
checked  bleeding  of  a  really  serious  nature.  I  know 
of  one  instance  where  it  did  seem  to  stop  a  most  dan- 
gerous post-operative  general  ooze  from  mucous  sur- 
faces in  a  deeply  jaundiced  patient,  but  I  know  of 
many  cases  where  it  utterly  failed.  And  horse  serum 
is  in  general  equally  valueless,  although  it  is  repeat- 
edly given  in  many  and  various  forms  of  bleeding.  In 
a  recent  case  of  hemorrhage  from  a  gastric  ulcer  six 
doses  at  from  three-  to  six-hour  intervals  were  totally 
unavailing.  Even  human  serum  is  fast  losing  favor, 
although  it  certainly  is  more  efficacious  than  animal 
serum.  Held  in  high  esteem  in  checking  the  bleeding 
of  the  new-bom,  melasna  neonatorum,  it  has  of  late 
been  found  sadly  wanting.  Only  a  few  months  ago, 
in  one  of  my  cases  15  c.c.  were  given  at  the  first  sign 
of  bleeding,  with  no  effect  whatsoever.  It  does  help 
occasionally,  but  too  much  reliance  cannot  be  placed 
upon  it.  Tissue  extract  and  fresh  human  tissue  are 
of  certain  service  if  applied  directly  to  bleeding  sur- 
faces, but  the  field  for  this  is  decidedly  limited.  Cal- 
cium lactate  need  hardly  be  mentioned.  It  is  of  no 
use  once  bleeding  has  started,  and  as  a  prophylactic  it 
is  of  doubtful  value. 

As  a  general  rule,  a  quarter  grain  of  morphia  is 
indicated  at  the  start  of  any  hemorrhage  to  quiet  the 


88  BLOOD  TRANSFUSION 

restlessness ;  after  that  the  doses  had  better  be  smaller 
because  of  the  depressant  effect  of  this  drug  on  respi- 
ration and  blood-pressure.  Measures  to  stop  the  bleed- 
ing should  be  instituted  immediately,  the  body  should 
be  kept  as  warm  as  possible,  the  foot  of  the  bed  ele- 
vated, the  limbs  bandaged  if  it  seems  advisable,  the 
patient  kept  quiet  and  fluids  given  ad  Uhitum,  liquids 
of  any  and  all  sorts,  by  mouth,  per  rectum,  subcutane- 
ous infusion,  intravenously — coffee,  tea,  water,  salt 
solution,  ice — anything  at  all  that  will  quench  the  in- 
tolerable thirst  and  keep  up  the  bulk  of  the  circu- 
lating medium — all  within  reason.  And  here,  per- 
haps, I  may  be  permitted  to  sound  a  note  of  warning — 
too  much  has  been  expected  of  salt  solution.  The 
custom  of  giving  salt  solution  (or  water)  per  rectum 
after  an  operation  of  any  magnitude  is  a  good  one 
and  the  salt  infusion  in  cases  of  bleeding  is  also  good, 
as  is,  at  times,  intravenous  salt — all  within  reason. 
But  it  is  ridiculous  in  the  extreme  to  keep  filling  a 
patient  full  of  salt  solution  just  because  a  great  quan- 
tity of  blood  has  been  lost.  Salt  solution  will  not  turn 
into  blood,  yet  it  is  all  but  expected  to  do  so. 

If  I  have  seen  one,  I  have  seen  a  dozen  patients 
actually  waterlogged  by  salt  solution,  and  with  no 
improvement  whatsoever.  It  never  seems  to  occur 
to  some  men  that  a  heart  can  be  overdistended,  that 
the  blood  can  be  made  too  dilute,  that  if  1000  c.c.  or 


CONTROL  OF  HEMORRHAGE  39 

1500  c.c.  of  salt  solution  do  no  good,  a  greater  amount 
will  be  equally  valueless.  But  time  and  time  again 
I  have  seen  infusions  repeated  after  2000  c.c.  of  salt 
have  been  taken  up  without  any  benefit  at  all.  Every- 
one knows  it  is  proper  to  give  salt  solution  in  cases  of 
blood  loss,  but  very  few  stop  to  consider  how  much 
ought  to  be  given.  Some  three  years  ago  I  was  asked 
to  see  an  old  gentleman  of  sixty-five  who  had  had  a 
suprapubic  prostatectomy  done.  He  went  off  the 
table  in  very  good  shape,  but  a  few  hours  later  began 
to  bleed  and  had  to  be  repacked.  Even  this  did  not 
stop  the  ooze,  so  about  four  or  five  hours  after  the 
operation  he  was  taken  to  the  operating  room  and 
thoroughly  packed  under  light  gas  anaesthesia.  Rather 
shocked  from  this  procedure  but  still  in  fair  condition, 
he  was  returned  to  his  bed  and  readily  took  up  2000  c.c. 
of  salt  solution.  In  spite  of  this  he  gradually  became 
weaker  and  finally  developed  a  Cheyne- Stokes  form 
of  respiration.  When  I  saw  him  his  blood-pressure 
was  around  70  mm.  and  he  was  in  a  semiconscious  con- 
dition. Those  in  charge  wished  to  delay  because  he 
was  taking  up  the  fluids  so  well,  but  gave  in  after  a 
brief  argument.  On  incising  his  arm  for  a  direct  trans- 
fusion, not  a  drop  of  blood  flowed  from  his  tissues,  but 
clear  serum  (salt  solution)  flowed  very  freely.  The 
introduction  of  a  few  hundred  c.c.  of  blood  from  his  son 
saved  his  life ;  and  curiously  enough  the  Cheyne- Stokes 


40  BLOOD  TRANSFUSION 

fomi  of  respiration  disappeared  while  the  blood  was 
actually  flowing  into  him. 

It  should  be  generally  understood  that  if  the  bleefd- 
ing  Ifas  not  been  too  great  a  few  hundred  c.c.  of  salt 
are  all  that  is  needed  to  tide  a  patient  over  a  dangerous 
period.  In  cases  of  very  s^evere  hemorrhage  the 
amount  might  be  increased  a  bit,  but  if  1000  to  1500 
C.C.  do  not  steady  a  falling  blood-pressure  or  cause  a 
slight  rifife,  its  introduction  had  better  be  discontinued. 
Even  where  there  has  been  a  rise,  the  greatest  caution 
must  be  exercisefd,  for  be  it  remembered  that  in  these 
desperate  conditions  salt  solution  will  frequently  cause 
a  rise  in  blood-pressure  but  will  not  sustain  it.  Where 
the  bleeding  has  been  excessive,  a  transfusion  of  blood 
is  indicated  because  it  has  been  conclusively  shown 
that  biood  alone  can  raise  a  pressure  and  sustain  it. 
Salt  solution  has  no  sustaining  power  per  se,  and 
when  the  fall  comes  after  a  rise  from  this  means  it 
usually  portends  the  end,  for  added  salt  solution  is 
useless.    It  never  raises  a  pressure  twice! 

As  the  result,  then,  of  blood  transfusion,  we  have 
been  able  to  really  study  the  phenomenon  of  hemor- 
rhage for  the  first  time,  and  we  have  learned  the  value 
of  doing  as  little  as  possible  in  the  condition.  Rest, 
quiet,  attempts  to  check  the  bleeding  by  mechanical 
means,  an  ice-bag  over  or  as  near  to  the  site  of  bleeding 
as  possible,  a  bit  of  morphine  for  the  restlessness  occa- 


CONTROL  OF  HEMORRHAGE  41 

sioned  by  the  condition,  and  salt  solution  and  we  have 
the  entire  armamentarium  for  treating  bleeding.  For 
we  have  learned  that  the  body  itself  does  more  toward 
checking  hemorrhage  than  can  be  done  by  outside 
means,  by  automatically  lowering  its  own  blood-pres- 
sure and  thereby  causing  a  slowing  of  the  circulation 
and  renewed  opportunity  for  coagulation  of  the  blood 
at  the  site  of  leakage.  But  the  more  I  see  of  hemor- 
rhage and  anaemia  in  general,  the  more  am  I  convinced 
of  the  utter  futility  of  having  a  specific  rule  by  which 
to  be  rigidly  governed.  Each  case  is  a  study  unto 
itself,  each  individual  represents  an  entity  which  «iust 
be  judged  from  all  angles,  and  experience  in  the  con- 
dition must  have  a  great  deal  of  weight  in  the  ultimate 
decision  as  to  the  course  to  pursue.  It  is  advisable, 
though,  to  have  some  tentative  plan  of  procedure  in 
cases  of  hemorrhage,  and,  since  there  are  certain  fun- 
damental features  common  to  a  degree  to  all  cases,  it 
is  possible*  to  formulate  a  working  rule.  For  instance, 
a  sudden  loss  of  blood  is  a  much  more  serious  matter 
than  a  gradual  depletion  and  a  rapidly  falling  blood- 
pressure  is  always  a  warning  of  value,  though  it  must 
be  remembered  that  nausea  of  the  slightest  degree 
will  affect  this  piiase  of  the  situation.  But  these  two 
features  really  are  dependable  in  the  majority  of  in- 
stances and  experience  has  demonstrated  that  a  good 
working  rule  is  to  transfuse  if  the  blood-pressm*e  falls 


4«  BLOOD  TRANSFUSION 

as  low  as  70  mm.  of  mercury,  since  life  is  hardly  pos- 
sible with  anything  below  this  limit.  In  some  in- 
stances, if  the  physician  or  surgeon  in  charge  of  the 
case  has  not  taken  the  steps  usual  in  emergency  cases 
it  may  be  wise  to  delay  until  these  can  be  instituted — 
preparation  for  transfusion  being  made  in  the  interval. 
If  the  actual  bleeding  has  been  checked,  if  the  patient 
is  quiet,  if  salt  solution  has  been  given  in  the  proper 
manner,  and  the  blood-pressure  still  remains  around 
70  with  the  tendency  to  flutter  a  little  below  this  point, 
it  may  be  assumed  that  the  case  is  utterly  hopeless, 
unless  new  blood  is  introduced ;  and  procrastination  at 
this  stage  of  the  game  is  a  fearfully  dangerous  plan, 
as  the  following  story  illustrates : 

In  the  Fall  of  1915  I  was  called  to  see  a  woman 
who  had  had  a  placenta  praevia,  and  had  been  de- 
livered in  the  manner  usual  for  such  conditions,  a 
large  amount  of  blood  being  lost,  though  not  nearly 
enough,  according  to  the  obstetrician  in  charge,  to 
have  caused  the  terrific  shock  that  ensued.  The  usual 
measures  to  combat  such  a  condition  had  been  carried 
out  before  I  reached  the  hospital.  When  I  first  saw 
her,  the  patient  was  in  a  semiconscious  condition, 
breathing  was  very  shallow,  her  pulse  very  rapid,  and 
her  pressure  around  70  mm.  The  obstetrician  in 
charge  of  the  case,  however,  felt  that  in  the  fifteen 
minutes  prior  to  my  coming  there  had  been  a  slight 


CONTROL  OF  HEMORRHAGE  43 

improvement,  and  the  blood-pressure  readings  ap- 
peared to  corroborate  this,  so  that  it  seemed  as  if  the 
condition  might  be  due  more  to  shock  than  to  hemor- 
rhage, and  that  if  left  alone  the  patient  might  recover 
without  transfusion.  We  waited  just  a  half  hour,  but 
during  those  thirty  minutes  we  lost  our  only  chance, 
for  suddenly  the  blood-pressure  dropped  still  further, 
the  patient  became  absolutely  unconscious  and  died 
just  as  the  transfusion  was  started. 

But  we  must  not  fall  into  the  habit  of  adhering 
too  closely  to  the  blood-pressure  for  guidance,  because 
it  is  not  absolutely  constant  and  at  times,  in  cases  of 
extreme  danger,  it  never  reaches  the  lowest  level,  or 
at  least  it  never  reaches  that  until  actual  exitus  is 
imminent.  For  instance,  in  September,  1916,  I  was 
asked  to  see  a  man  who  had  been  bleeding  from  an 
obscure  intestinal  condition  for  over  twenty-four 
hours.  He  had  passed  tremendous  quantities  of  blood 
and  looked  quite  ill,  yet  his  blood-pressure  reading 
when  I  saw  him  was  136  mm.  Being  a  man  of  fifty- 
one,  that  was,  perhaps,  a  little  low,  but  no  one  who 
has  a  pressure  of  136  mm.  is  in  any  danger  of  dying 
from  brain  anaemia  under  ordinary  circumstances. 
And  another  curious  feature  of  this  same  case  was 
that  his  hsemoglobin  registered  68  per  cent.  No  better 
illustration  could  possibly  be  had  of  the  points  I  have 
been  making  in  this  chapter  than  this  single  case. 
The  question  arose  as  to  what  to  do.    He  had  been 


44  BLOOD  TRANSFUSION 

given  horse  serum  repeatedly  with  no  apparent  effect 
on  the  bleeding,  and,  while  he  looked  quite  ill  and 
those  in  attendance  felt  that  he  was  almost  surely  be- 
yond help,  I  could  not  feel  that  he  was  in  any  im- 
minent danger  and  therefore  decided  to  study  the 
case  further,  in  the  meantime  testing  out  donors  in 
ease  transfusion  should  become  necessary.  Two 
hours  after  I  first  saw  him  he  had  another  huge  hemor- 
rhage from  the  bowel  and  his  pressure  dropped  ten 
points  while  his  haemoglobin  dropped  eight  points. 
The  man  at  this  time  looked  desperately  ill,  and  in 
spite  of  the  fact  that  he  had  a  blood-pressure  well 
within  the  usual  limits  of  safety  and  a  haemoglobin 
quite  well  up  in  the  schedule,  I  decided  upon  and 
carried  out  an  immediate  transfusion.  From  the 
moment  blood  was  introduced  the  patient's  condition 
improved  and  he  never  bled  another  drop.  His  sub- 
sequent history  has  revealed  the  fact  that  the  condi- 
tion was  a  duodenal  ulcer. 

A  survey  of  the  foregoing  pages  leads  one  to  the 
•onclusion  that  many  considerations  enter  into  a  de- 
termination as  to  the  wisest  course  to  pursue  in  con- 
trolling severe  bleedings.  Conservative  tactics  are  in 
order  so  long  as  actual  danger  limits  are  not  in  evi- 
dence, but  it  has  been  conclusively  shown  that  one 
must  be  most  guarded  in  concluding  that  this  point 
has  not  been  reached,  since  all  signs  may  be  deceptive 


CONTROL  OF  HEMORRHAGE  4i> 

and  a  false  security  may  have  come  about  through  the 
unwise  use  of  ineffectual  drugs,  especially  opiates.  It 
has  been  further  demonstrated  that  the  use  of  salt 
solution  in  all  conditions  of  hemorrhage  is  most  help- 
ful if  care  is  exercised,  but  that  its  indiscriminate 
employment  is  fraught  with  grave  danger  and  fre- 
quently results  in  taking  away  from  the  patient  what 
little  chance  he  may  have  had  by  over-distending  the 
heart,  over-diluting  the  blood  or  actually  waterlogging 
his  tissues.  But  a  working  rule  has  been  suggested 
based  upon  the  two  features  most  dependable  and 
constant  in  dangerous  hemorrhages — namely,  the 
rate  of  blood  loss  and  blood-pressure  readings,  a  base 
line  of  70  mm.  of  mercury  being  assumed  as  an  indi- 
cation for  immediate  blood  transfusion  regardless  of 
all  other  features  of  the  case. 

REFERENCES 

Bernheim,  B.  M. :  "  The  Limits  of  Bleeding  Considered  from 
the  Clinical  Standpoint."  Am.  Journ.  Med.  Sciencet, 
April,  1917. 

Bloodgood,  J.  C. :  "  Studies  in  Blood-pressure  Before,  Dur- 
ing and  After  Operations  with  Reference  to  the  Early 
Recognition,  Prevention  and  Treatment  of  Shock." 
Armals  of  Surgery,  December,  1913. 

Crile,  G. :  "  Hemorrhage  and  Transfusion,"  1909. 

David,  V.  C,  and  Curtis,  A.  H. :  "  Exj>eriments  in  the  Treat- 
ment of  Acute  Anasmia  by  Blood  Transfusion  and  bj 
Intravenous  Saline  Infusion."  Surg.,  Gyn.  and  Obstet- 
rics, October,  1912. 

Litchfield,  L.:  "The  Abuse  of  Normal  Salt  Solution." 
J.  A.  M.  A.,  1914. 


CHAPTER  IV 

INDICATIONS  FOR  TRANSFUSION 
In  the  early  days  of  transfusion,  when  it  was  a 
real  ordeal  to  accomplish  the  blood  transfer,  indica- 
tions for  the  procedure  were  limited  practically  to 
hemorrhages  of  the  most  exsanguinating  variety  and 
to  anaemias  of  such  grade  that  recovery  or  improve- 
ment without  added  blood  was  utterly  impossible. 
But  the  technic  of  the  operation  has  undergone  a 
gradual  evolution  imtil  now  it  is  so  uninvolved,  so 
readily  accomplished,  that  its  field  of  usefulness  has 
broadened  enormously  and  bids  fair  to  spread  still 
further,  and  now  transfusions  are  carried  out  where 
there  are  no  true  indications  at  all,  strictly  speaking, 
the  mere  possibility  of  benefitting  a  condition  by  the 
addition  of  blood  being  considered  sufficient  warrant. 
In  other  words,  transfusion  of  blood  was  used  formerly 
purely  as  a  life-saving  means,  a  heroic  last  resort, 
while  now  it  not  only  fulfils  this  purpose  to  an  even 
better  degree  than  formerly  but  has  taken  on  the 
added  importance  of  therapeutic  usefulness,  which  at 
once  opens  up  possibilities  and  opportunities  hereto- 
fore inconceivable. 

Any    absolute    tabulation    of    indications    under 
46 


INDICATIONS  FOR  TRANSFUSION  47 

present-day  conditions  when  transfusion  is  still  in  a 
process  of  evolution  must  be  taken  as  subject  to 
revision,  as  the  future  will  very  likely  see  its  use  in 
maladies  not  at  present  under  consideration  and  its 
disuse  in  conditions  for  whose  relief  it  is  now  em- 
ployed. FurtheiTnore,  it  must  be  understood  that 
absolute  indications  do  not  exist  for  transfusion  in 
the  same  sense  that  they  do  for  other  surgical  pro- 
cedures such  as,  for  example,  an  appendectomy  for 
an  acute  appendicitis  or  a  radical  amputation  of  the 
breast  for  a  carcinoma.  The  reason  for  this  is  that 
manj^  times  a  transfusion  is  done  for  a  phase  encoun- 
tered, in  the  course  of  some  acute  or  chronic  illness 
rather  than  for  the  elimination  or  relief  of  some 
definite  pathological  entity,  and  since  this  phase 
amounts  to  a  depletion  of  the  circulating  medium  of 
the  body  resulting  from  accident  or  disease,  no  abso- 
lute indication  can  be  possible  because  of  our  inability 
— at  the  present  time — to  determine  actual  limits  of 
blood  loss.  We  may  say  that  the  introduction  of 
blood  is  indicated  in  all  exsanguinating  hemorrhages, 
but  in  making  such  a  statement  it  must  be  understood 
that  there  is  an  implied  reservation,  for  one  must  be 
able  to  judge  which  hemorrhage  of  the  exsanguinat- 
ing variety  will  prove  fatal  without  transfusion,  since 
the  term  exsanguinating  is  used  rather  loosely  and 
does  not  always  indicate  a  fatal  hemoiThage. 


48  BLOOD  TRANSFUSION 

This  distinction  between  indications  for  transfusion 
and  for  certain  other  operations  may  seem  more 
fanciful  than  real,  but  one  has  only  to  engage  in  the 
work  for  a  brief  time  to  realize  its  truth.  There  can  be 
no  more  difficult  problem  at  times  than  a  determination 
as  to  when  a  transfusion  is  or  is  not  indicated,  nor  can 
a  more  embarrassing  or  dangerous  situation  arise  than 
where  an  honest  difference  of  opinion  exists  between 
medical  advisers,  with  the  patient's  life  hanging  in 
the  balance.  The  oft-repeated  saying  that  the  public 
ward  patients  fare  best  because  they  do  not  suffer 
from  prolonged  consultations  between  a  number  of 
medical  advisers  is  especially  applicable  in  transfusion 
work;  their  condition  is  sized  up  with  as  little  delay 
as  possible  and  the  proper  measiu'es  for  relief  are 
instituted  at  once,  while  there  is  a  tendency  to  delay 
matters  in  the  case  of  the  so-called  private  patient. 

Obviously  it  would  be  unwise  to  transfuse  all 
patients  who  have  suffered  a  terrific  hemorrhage,  be- 
cause the  majority  of  them  recover  without  it.  A 
somewhat  similar  state  of  affairs  exists  with  regard 
to  other  conditions,  such  as,  for  example,  haemophilia, 
melaena  neonatorum,  bleeding  from  jaundice,  et 
cetera,  though  in  a  different  way.  Transfusion  would 
probably  stop  the  bleeding  in  nearly  every  case  and  one 
might  conclude  that  it  is  therefore  indicated,  but  there 
are  other  measures  which  are  sometimes  indicated 


INDICATIONS  FOR  TRANSFUSION  49 

prior  to  transfusion,  such  as  the  injection  of  serum  or 
the  subcutaneous  injection  of  whole  blood  or  the  use  of 
calcium.  So  that  the  question  of  indication  is  a  com- 
plex one  for  not  alone  must  one  decide  as  to  whether  or 
not  the  procedure  is  indicated,  he  must  further  deter- 
mine when  it  is  indicated.  If  a  severe  traumatic  hemor- 
rhage is  under  consideration  and  certain  operative 
measures  must  be  carried  out,  those  in  charge  of  the 
case  must  be  able  to  decide  as  to  whether  the  trans- 
fusion should  be  done  prior  to  them,  during  their 
course,  or  afterwards.  Or  if  an  infant  is  suffering 
from  melaena  neonatorum,  it  will  not  suffice  to  say 
that  transfusion  is  indicated  but  the  serum  treatment 
should  be  tried  first  just  because  injected  serum  will 
stop  the  bleeding  in  a  certain  proportion  of  the  cases. 
It  may  be  that  the  case  in  hand  has  progressed  too  far, 
that  simple  cessation  of  the  bleeding  is  not  enough 
and  therefore  transfusion  should  be  done  without  pre- 
liminary serum  treatment  in  order  to  accomplish  the 
double  purpose  of  stopping  the  bleeding  and  com- 
bating the  profound  anaemia. 

Hard  and  fast  rules  cannot  be  drawn.  One  must 
be  guided  by  the  single  purpose  of  doing  the  most 
good  with  the  minimum  of  risk.  If  a  difference  of 
opinion  exists  as  to  the  advisability  or  necessity  of  a 
transfusion,  it  is  best  to  postpone  the  operation  if 
the  patient  is  in  no  imminent  danger,  because  the  re- 


60  BLOOD  TRANSFUSION 

cuperative  powers  of  the  human  body  are  such  that 
many  recoveries  come  about  unaided  in  conditions  that 
seem  hopeless  at  first  sight.  On  the  other  hand,  a 
patient  in  imminent  danger  ought  not  to  be  subjected 
to  unnecessary  delay.  I  hardly  think  that  any  great 
number  of  unnecessary  transfusions  are  carried  out, 
but  I  am  convinced  that  many  cases  are  lost  either  by 
not  transfusing  at  all  or  by  doing  it  too  late.  And 
not  only  this,  there  are  many,  many  cases  whose  illness 
could  be  materially  shortened  by  the  introduction  of 
blood,  whose  operations  could  be  made  less  hazardous, 
whose  whole  after-course  could  be  made  less  burden- 
some. 

With  this  preliminary  survey,  then,  it  seems  war- 
rantable to  formulate  the  following  list  of  probable 
indications  ^ : 

I.  Transfusions  for  actual  hemorrhage: 

(fl)   Traumatic. 

(&)   Gastric  and  duodenal  ulcer. 

(c)  Post-partum. 

(d)  Ruptured  ectopic  pregnancy. 

(e)  Typhoid  hemorrhage. 

II.  Transfu^ons   in    connection   with   surgical 
operations: 

^  I  have  followed  very  closely  the  classification  of  Libman 
and  Ottenberg,  as  given  in  the  reference  appended  at  the 
back  of  the  chapter. 


INDICATIONS  FOR  TRANSFUSION  51 

(a)   Preliminary  to,  during  or  just  after 

operation, 
(fc)   For  post-operative  hemorrhage. 

(c)  For  post-operative  shock. 

(d)  For  post-operative  ansemia  and  pros- 
tration. 

III.  Transfusions  for  the  relief  of  hemorrhagic 
conditions: 

(a)  Purpura  hemorrhagica. 

(b)  Hasmophiha. 

(c)  Hemorrhages  secondary  to  (1)  blood 
diseases,  (2)  severe  infections,  (3) 
jaundice,   (4)  idiopathic  uterine. 

IV.  Transfusions  for  blood  disease: 

(a)   Pernicious  anaemia, 
(c)   Leukaemia. 
V.  Transfusions  for  infections: 

(a)   Infections  with  pyogenic  orgamsms. 

(c)  Subacute  streptococcus  endocarditis. 

(d)  Subacute    infection    of    any    nature 

other  than  septicaemia. 
VI.  Transfusions  for  intoxications  and  poisonings: 

(a)  Toxaemia  of  pregnancy. 

(b)  Eclampsia. 

(c)  Uraemia. 

{d)   Benzol  poisonmg. 

(e)  Illuminating  gas  poisoning. 


62  BLCX)D  TRANSFUSION 

VII.  TransfvMons  for  debilitated  conditions: 
(a)   Cancer. 
(h)   Malnutrition, 
(c)    Simple  anaemia  from  any  cause. 

Subsequent  chapters  will  consider  these  various 
conditions  in  detail. 

REFERENCES 

Bemheim,  B.  M. :  "  Therapeutic  Possibilities  of  Transfu- 
sion." J.  A.  M.  A.,  July  26,  1913. 

Bemheim,  B.  M. :  "  The  Limits  of  Bleeding  Considered  from 
the  Clinical  Standpoint."  Am.  Journ.  Med.  Sciencet, 
April,  1917. 

Miller,  G. :  "  Blood'  Transfusion,  Indications  and  Technique." 
Medical  Record,  September  11,  1916. 

Ottenberg,  R.  and  Libman,  E. :  "Blood  Transfusion;  Indi- 
cations; Results;  General  Management."  Am.  Journal 
Med.  Sciences,  1916,  cl,  36-69. 


CHAPTER  V 

DANGERS  OF  TRANSFUSION.    HEMOLYSIS  AND 
AGGLUTINATION 

That  quite  a  few  lives  have  been  lost  through 
transfusion  cannot  be  denied,  but  that  most  of  the 
fatalities  have  resulted  from  inexperience  and  oc- 
curred in  the  early  days  of  the  procedure  is  equally 
true.  In  reviewing  the  statistics  on  this  work,  it  must 
be  remembered  that  certain  of  its  most  important 
features  have  come  to  be  clearly  understood  only 
within  the  last  few  years,  and  that  its  results  are 
sometimes  influenced  by  the  extraordinary  circum- 
stances under  which  much  of  it  must  be  carried  out. 

In  1914  I  sent  out  a  questionnaire  to  twenty  men 
who  were  actively  engaged  in  transfusion  work,  ask- 
ing for  their  opinion  and  experience  in  regard  to  its 
dangers.  This  was  done  in  order  to  be  able  to  set 
before  the  profession  the  absolute  facts  in  a  matter 
that  had  hitherto  been  dealt  with  only  in  generalities, 
in  spite  of  the  fact  that  accurate  knowledge  was  of 
prime  importance.  From  the  fourteen  replies,  the 
following  facts  were  deduced:  In  800  transfusions 
there  occurred  fifteen  cases  of  macroscopic  hsemoglo- 
binuria  (an  incidence  roughly  of  2  per  cent.)  with 

53 


64  BLOOD  TRANSFUSION 

eleven  recoveries  and  four  deaths.'  Six  of  these  trans- 
fusions were  done  for  tuberculosis,  no  deaths ;  two  for 
post-operative  hemorrhage,  one  death;  and  one  for 
haemophilia,  no  deaths.  In  three  of  the  deaths,  no 
hemolytic  tests  were  made,  although  there  was  plenty 
of  time  to  do  so  in  two  of  the  cases,  the  conditions 
being  lymphatic  leukaemia  and  pernicious  anaemia. 
The  third  case  was  an  extremely  hurried  emergency, 
my  own  case.  In  the  case  of  the  fourth  death,  tests 
were  made,  and  it  was  known  prior  to  operation  that 
"  the  donor's  cells  were  slightly  agglutinated  by  the 
patient's  serum."  But  it  was  necessary  to  use  this 
donor  because  no  other  was  available,  and  since  agglu- 
tination is  an  entirely  different  process  from  haemoly- 
sis— which  was  negative  in  the  tests — it  was  evidently 
considered  safe  to  use  the  donor  under  the  circum- 
stances. A  similar  predicament  arose  in  my  second 
case,  in  which  tests  revealed  slight  haemolysis  (no 
agglutination)  of  the  donor's  corpuscles  by  the  serum 
of  the  recipient.  No  other  donor  was  available  and  the 
transfusion  seemed  most  desirable,  even  essential  to  the 
success  of  an  exploratory  operation  and  pyloroplasty 
in  a  man  almost  exsanguinated  from  a  bleeding  gastric 
ulcer.  Besides,  I  had  been  under  the  impression  from 

^  One  of  the  men  who  failed  to  answer  reported  in  the 
J.  A.  M.  A.  for  March,  1914,  a  series  of  135  transfusions 
with  three  instances  of  htemolvsis.    All  three  cases  recovered. 


DANGERS  OF  TRANSFUSION  55 

statements  from  various  som-ces  that  haemolysis  in  vivo 
did  not  necessarily  follow  its  occurrence  in  vitro. 
Perhaps  this  is  so,  but  I  will  never  again  take  any 
unnecessary  chances.  This  patient  had  a  well-marked 
heemoglobinuria  within  twelve  hours  after  transfusion, 
as  a  consequence  of  which  he  suffered  a  marked  fall  in 
haemoglobin,  losing  practically  all  the  blood  we  gave 
him.  His  recovery  is  probably  due  to  the  fact  that 
his  serum  was  only  very  slightly  lytic,  and  that,  know- 
ing the  danger  we  ran,  we  transfused  a  minimal 
amount  of  blood — ^just  sufficient  to  tide  him  over  his 
operation.  Whether  he  really  derived  any  benefit,  in 
view  of  his  hsemolysis,  is  a  debatable  question  which 
need  not  be  considered  here. 

Proceeding  with  the  study  of  these  fifteen  cases  of 
haemolysis,  in  the  eleven  recoveries,  tests  were  made  in 
nine  instances  and  haemolysis  prognosticated,  evidence 
quite  sufficient  to  indicate  the  value  of  tests  when 
properly  made.  That  there  were  no  fatalities  in  these 
nine  instances  is  a  purely  accidental  circumstance.  In 
one  other  instance  besides  my  own,  the  patient's  serum 
was  lytic  to  donor's  cells — that  is,  the  patient's  serum 
simply  destroyed  the  red  cells  introduced  into  the  cir- 
culation. The  exact  test  contraindication  was  not 
mentioned  in  the  other  seven  cases,  but  in  the  two  men- 
tioned it  must  be  assumed  that  the  patient's  recovery 
can  be  ascribed  to  the  fact  that,  since  the  foreign  cor- 


M  BLOOD  TRANSFUSION 

puscles  alone  were  destroyed,  a  quantity  of  them,  in- 
sufficient to  cause  death  when  broken  up  with  the 
resultant  liberation  of  their  haemoglobin,  was  intro- 
duced at  transfusion.  Had  conditions  been  reversed — 
that  is,  had  donor's  serum  been  lytic  to  recipient's  cor- 
puscles or,  in  other  words,  had  the  patient's  own  cor- 
puscles been  liable  to  destruction — there  would  have 
been,  in  all  probability,  two  more  deaths  to  chronicle. 

So  long  as  the  whole  blood  was  used  the  method  of 
transfusion  employed,  direct  or  indirect,  appeared  to 
be  immaterial.  In  the  list  of  indirect  transfusions, 
however,  there  were  about  sixty  in  which  defibrinated 
blood  was  used.  One  sudden  death  resulted  in  this 
series,  and  I  have  knowledge  of  one  other  death  (not 
reported)  from  a  similar  cause.  It  seems  that  the  use 
of  defibrinated  blood  introduces  into  transfusion  a 
factor  that  does  not  occur  when  the  whole  blood  is 
used.  This  factor  is  both  obscure  and  dangerous,  and 
since  the  transfer  of  whole  blood  is  even  simpler  than 
that  of  the  whipped  variety,  I  have  been  at  a  loss  to 
understand  why  any  one  should  persist  in  employing 
the  latter.  Prejudice  or  habit  may  be  the  cause,  but 
the  patient's  welfare,  at  least,  should  be  shown  some 
consideration. 

There  were  six  fatalities  due  to  causes  other  than 
haemolysis,  four  from  acute  dilatation  of  the  heart  and 
two  from  questionable  anaphylaxis. 


DANGERS  OF  TRANSFUSION  57 

Seven  of  the  surgeons  considered  hsemolysis  to  be 
the  chief  danger  of  transfusion — one  man  volunteer- 
ing the  information  that  he  personally  knew  of  three 
unpublished  deaths  from  this  cause.  One  considered 
this  the  second  chief  cause,  while  two  saw  no  danger 
in  it  under  any  circumstances  and  made  no  tests! 
Three  men  regarded  acute  dilatation  of  the  heart  as 
the  chief  danger,  while  four  looked  upon  this  as  the 
second  chief  factor,  six  disregarding  it  entirely. 
One  man  considered  embolism  the  chief  danger,  and 
one  sepsis,  because  frequently  the  operation  must  be 
hurried. 

Of  course,  we  are  all  more  prone  to  report  our 
successes  than  our  failures,  so  that  a  considerable 
number  of  accidents  and  fatalities  in  the  course  of 
transfusions  must  be  reckoned  as  having  occurred 
without  being  reported.  I  personally  know  of  sev- 
eral, and  verbal  reports  of  others  have  been  brought  to 
my  attention;  but  further  experience  in  the  work,  and 
communication  with  colleagues  have  convinced  me 
that  the  above  report  still  remains  approximately  cor- 
rect. If  anything,  an  improvement  in  results  can  be 
counted  on,  because  with  the  diminishing  popularity 
of  direct  transfusion,  the  danger  of  overdistention  of 
the  right  side  of  the  heart  coincidently  has  decreased, 
and  with  the  more  general  knowledge  of  the  latent 
possibilities  of  hsemolysis  and  agglutination,  labora- 


58  BLOOD  TRANSFUSION 

tory  tests  for  matching  up  bloods  prior  to  transfusion 
have  become  the  rule  rather  than  the  exception. 

The  only  two  features  that  may  possibly  keep  the 
average  accident  mortality  figures  where  they  were  or 
raise  them  a  bit,  are,  first,  the  more  widespread  use  of 
transfusion  by  the  profession  at  large  and  the  conse- 
quent inexperience  of  many  operators  and,  second,  the 
recent  practice  of  adding  chemicals  to  the  blood  in 
order  to  retard  coagulation.  Time  will  doubtless  re- 
move both  of  these  complications,  but  an  unbiased  view 
compels  the  recognition  of  certain  accidents  and  deaths 
that  have  necessarily  occurred  in  the  development  of 
the  recent  and  promising  citrate  technic  of  transfusion. 

What,  then,  do  we  mean  by  dangers  of  transfusion 
and  how  may  they  be  recognized  and  avoided?  To 
consider  them  in  their  logical  order,  an  overdistention 
of  the  heart  can  occur  only  in  one  way — inflow  of  a 
liquid  whose  pressure,  rate  and  volume  are  greater 
than  can  be  cared  for  by  the  right  ventricle  of  the 
heart,  and  this  can  occur  when  the  fluid  is  running 
in  of  its  own  accord,  as  in  a  direct  transfusion  or  an 
ordinary  intravenous  infusion  of  salt  solution,  or  when 
the  liquid  is  being  injected  by  needle  and  syringe.  It  is 
an  ever-present  danger  that  can  be  avoided  only  b}'' 
constant  watchfulness  on  the  part  of  operator  and 
assistants,  for  it  must  be  remembered  that  in  practi- 
cally every  instance  of  transfusion,  the  blood  pressure 


DANGERS  OF  TRANSFUSION  59 

of  the  patient  it  quite  low — usually  much  lower  than 
normal — so  that  the  pressure  of  the  inflow  must  be 
regulated  accordingly,  that  is,  it  must  be  a  little,  but 
not  too  much,  higher  than  the  intake  side. 

Hearts  vary,  too,  quite  markedly  in  their  ability 
to  accommodate  an  unusual  inflow.  A  young  indi- 
vidual who  has  been  depleted  by  an  accidental  hemor- 
rhage ^vill  almost  never  be  embarrassed  by  a  rapid 
inflow  of  salt  solution  or  blood  because  his  heart  muscle 
is  young  and  strong  and  capable  of  standing  almost 
any  strain,  but  the  heart  of  that  same  young  man 
would  be  able  to  stand  very  little  had  he  been  through 
a  long  typhoid  struggle  during  the  course  of  which 
an  intestinal  hemorrhage  necessitated  the  introduction 
of  blood.  The  man  or  woman  of  fifty  or  sixty  whose 
heart  has  undergone  myocardial  changes  must  always 
be  watched  most  carefully.  Further,  we  must  keep  in 
mind  the  fact  that  transfusion  is  not  infrequently  done 
nowadays  for  the  relief  of  conditions  such  as  per- 
nicious anaemia,  where  the  trouble  is  apparently  only 
with  the  cellular  element  and  the  fluid  content  of  the 
blood  is  approximately  normal.  Under  such  circum- 
stances, with  the  vessels  filled  to  practically  their 
normal  capacity,  an  embarrassed  circulation  can  only 
be  avoided  by  a  most  circumspect  injection  of  liquid 
of  any  kind. 

The  signs  of  an  overdistended  right  heart  need  not 


00  BLOOD  TRANSFUSION 

be  unduly  dwelt  upon,  since  they  are  none  other  than 
those  of  a  broken  heart  compensation,  and  as  such  are 
familiar  to  all  medical  men.  The  slightest  nausea  in 
the  course  of  a  transfusion  should  serve  as  a  danger 
signal ;  blueness  of  the  lips  or  skin  is  an  added  warn- 
ing, as  is  a  cold  clammy  skin  upon  which  beads  of 
perspiration  break  out.  Given  in  addition  shortness 
of  breath,  a  rapid,  irregular  pulse  and  vomiting  and 
we  have  a  classical  picture  of  acute  dilatation — 
one  that  should  never,  under  any  circumstances,  be 
seen  during  the  course  of  this  work.  At  the  faintest 
sign  of  trouble  the  inflow  should  be  slackened  and 
its  pressure  diminished  and,  if  conditions  do  not 
promptly  improve,  the  transfusion  should  be  dis- 
continued until  the  heart  does  recover,  when  it  may 
be  most  gradually  resumed. 

So  much  for  the  patient  who  is  awake  or  con- 
scious. For  those  who  are  ansesthetized  or  are  un- 
conscious from  shock  or  any  cause  that  necessitates 
transfusion,  the  matter  becomes  more  complicated, 
since  there  remain  for  guidance  only  the  pulse,  color, 
and  respiration.  In  these  cases  a  stethoscope  strapped 
to  the  precordium  is  perhaps  the  most  trustworthy 
means  of  detecting  early  cardiac  distress,  but  an  alert 
anaesthetist  can  do  much  by  constant  watchfulness  of 
respiration  as  well  as  pulse.  The  inflow  of  blood 
should  be  slower  than  usual  and  one  should  err  on  the 


DANGERS  OF  TRANSFUSION  01 

side  of  giving  too  little  blood  rather  than  too  much 
under  these  circumstances. 

It  is  possible,  of  course,  to  give  a  general  infection 
in  the  course  of  a  transfusion  through  faulty  technic, 
and  doubtless  this  has  happened,  but  it  has  not  oc- 
curred in  my  series  of  cases,  and  I  am  happy  to  say 
that  no  instance  of  it  has  come  to  my  personal  atten- 
tion, although  I  have  indirect  knowledge  of  its  occur- 
rence. It  should  never  occur,  and,  in  view  of  the  sim- 
plicity and  rapidity  of  the  present-day  iodine  technic 
made  use  of  in  preparing  the  skin  for  surgical  inter- 
vention, only  the  grossest  blunders  could  give  rise  to  it. 

The  occurrence  of  an  embolus  during  transfusion 
is  recognized  but  is  very,  very  rare.  I  have  seen  it 
once — during  a  direct  transfusion — at  least,  in  one  of 
my  cases  signs  arose  which  could  be  attributed  only  to 
an  embolus;  but  since  the  patient  recovered  I  was 
unable  to  prove  it.  Theoretically,  instances  of  embol- 
ism ought  to  be  of  rather  frequent  occurrence,  but  one 
hardly  ever  sees  this  danger  even  mentioned.  I  do 
not  recall  seeing  a  single  report  of  it  in  the  literature, 
but  have  heard  of  one  case  which  recovered.  It  would 
seem  that  clots  which  occur  in  needles  and  tubes  during 
transfusion  are  not  friable  and  that  bits  of  them  do  not 
tend  to  wash  off,  as  might  be  supposed.  When  clot 
formation  begins,  it  adheres  firmly  to  the  side  of  the 
tube  or  needle  and  either  remains  there  or  increases 


62  BLOOD  TRANSFUSION 

in  size  till  it  occludes  the  lunien,  and  everyone  knows 
how  difficult  it  is  to  free  the  lumen  of  the  smaller 
needles  from  a  blood-clot.  It  takes  an  enormous 
amount  of  pressure,  in  fact  the  pressure  that  one  can 
get  from  a  20  c.c.  record  syringe  hardly  suffices,  and 
a  solid  piece  of  wire  must  usually  be  brought  into  play 
to  get  the  desired  result.  This  is  probably  the  reason 
why  emboli  do  not  occur. 

The  danger  of  transmitting  disease  by  transfusion 
is  real  but  fortunately  small.  Syphilis  is  about  the 
only  one  that  need  be  feared  and  if  careful  tests  are 
made  prior  to  transfusion,  as  should  be  done,  this 
danger  can  be  entirely  eliminated.  It  occasionally 
happens,  though,  that  time  to  do  the  tests  is  lacking  or 
there  are  no  facilities,  in  which  case  careful  physical 
examination  and  the  historj'^  must  be  relied  on.  I  have 
positive  knowledge  of  one  case  where  a  son  transmitted 
an  acquired  syphilis  to  his  father  who  was  suffering 
from  pernicious  ansemia.  The  boy  evidently  knew 
he  had  the  disease,  because  he  refused  to  have  his 
Wassermann  done  while  there  was  time.  The  father 
finally  took  a  sudden  turn  for  the  worse  and  an  emer- 
gency transfusion  was  done  from  his  son — with  dis- 
astrous consequences.  This  is  the  only  instance  of  this 
that  I  know  of,  but  since  its  occurrence,  I  have  insisted 
on  a  Wassermann  in  every  transfusion  not  of  an  emer- 
gency character,  whether  the  donor  is  a  relative  or 


DANGERS  OF  TRANSFUSION  6S 

not,  and  in  the  emergencies  I  try  to  rule  it  out  as  best 
I  can,  explaining  the  danger  to  the  relatives. 

I  have  once  transmitted  a  double  infection  of 
malaria  by  means  of  a  transfusion,  the  types  being 
that  of  tertian  and  sestivo-autumnal,  and  have  knowl- 
edge of  one  similar  occurrence  which  has  not  been 
reported  in  the  literature.  In  fact,  I  have  never  seen 
a  report  of  this  sort  in  all  the  voluminous  literature 
on  the  subject  of  transfusion  and  had  never  considered 
this  as  a  possibility,  since  it  had  been  my  impression 
that  the  mosquito  was  a  necessary  intermediary  in  the 
transmission  of  this  disease.  Since  the  undoubted 
occurrence  of  my  own  case,  however,  I  have  learned 
that  certain  Italian  workers  have  successfully  trans- 
mitted the  disease  by  blood  injection  not  once  but 
several  times.  My  case  occurred  early  in  1917  and 
is  unreported  at  the  present  writing,  but  the  details 
will  be  given  very  shortly. 

After  all  is  said,  the  only  real  danger  in  blood 
transfusion  is  that  resulting  from  haemolysis  and 
agglutination,  either  one  or  both  combined,  although, 
of  the  two,  haemolysis  is  far  the  more  frequent  in  occur- 
rence and  the  more  dangerous.  By  haemolysis  is  under- 
stood the  destruction  of  red  blood-corpuscles,  a  patho- 
logical phenomenon  that  always  occm's  when  bloods  of 
different  species  are  mixed  and  one  that  may  or  may 
not  come  to  pass  when  two  perfectly  normal  bloods  of 


64  BLOOD  TRANSFUSION 

the  same  species  are  mixed.  Its  exact  cause  is  un- 
known, but  in  the  case  of  two  humans  the  serum  of 
one  may  destroy  the  corpuscles  of  the  other  with  the 
consequent  setting  free  in  the  blood  stream  of  the 
haemoglobin  contained  in  them,  the  index  being  a  hse- 
moglobinuria,  since  the  liberated  haemoglobin  is  ex- 
creted by  the  kidneys.  A  very  mild  grade  of  haemolysis 
probably  occurs  every  time  a  transfusion  is  done  be- 
cause there  must  be  a  certain  minimal  cell  injury  and 
destruction  in  the  actual  handling  and  transfer  of  the 
blood  no  matter  what  method  is  used  or  how  great 
the  care,  for  blood  cells  are  so  delicate  that  even  mo- 
mentary contact  with  a  foreign  substance  like  a  tube 
or  needle  must  injure  them.  But  these  grades  are  of  no 
significance  as  far  as  is  known,  since  they  never  give 
rise  to  symptoms  and  never  cause  a  microscopic  or 
macroscopic  hsemoglobinuria.  Possibly  spectroscopic 
tests  would  reveal  the  presence  of  these  mild  grades, 
but  since  they  are  harmless  they  will  not  be  considered. 
The  grosser  grades,  though,  are  of  definite  sig- 
nificance and  usually  manifest  themselves  shortly  after 
the  conclusion  of  transfusion,  first  in  the  shape  of  a 
chill  followed  by  fever,  and  then  by  an  alarming  pros- 
tration of  greater  or  lesser  severity,  depending  upon 
the  amount  of  blood  destruction  taking  place.  Haemo- 
globin usually  makes  its  appearance  in  the  first  void- 
ing, being  diagnosed  by  the  reddish  brown  color  of  the 


DANGERS  OF  TRANSFUSION  65 

urine  and  a  sediment  like  reddish  brown  brick-dust. 
If  the  case  is  a  mild  one  the  urine  may  be  but  faintly 
colored,  and  only  one  voiding  may  contain  the  haemo- 
globin, as  happened  in  one  of  my  cases;  but  if  severe 
and  continued  blood  destruction  is  taking  place  the 
urine  becomes  progressively  darker  and  the  output 
diminishes  as  the  kidney  tubules  become  occluded  by 
deposits  of  haemoglobin  in  them.  In  a  fatal  case  of 
mine,  actual  cessation  of  kidney  excretion  gradually 
took  place,  the  patient  becoming  desperately  pros- 
trated and  exhibiting  all  the  signs  of  uraemia,  from 
which  she  died. 

It  would  seem  to  be  impossible  to  stop  the  trouble 
once  it  has  begun,  but  in  one  case  I  gave  a  500  c.c.  salt 
infusion  the  moment  haemoglobin  made  its  appearance 
in  the  urine,  and  a  prompt  cessation  took  place. 
Whether  this  was  because  of  the  infusion  or  in  spite 
of  it,  I  am  at  a  loss  to  say,  but  another  recent  case 
had  an  equally  happy  ending.  Most  likely  the  bloods  in 
these  two  cases  were  only  faintly  antagonistic,  but  a 
salt  infusion  can  do  no  harm,  and,  since  no  other  means 
of  combating  the  phenomenon  has  been  suggested,  it 
may  be  worth  trying.  Prevention  by  tests  is  of  course 
the  proper  thing,  but  the  first  case  in  question  had 
been  tested  and  reported  as  satisfactory.  Control  tests 
showed  them  to  have  been  faulty,  the  only  serious  error 

5 


M  BLOOD  TRANSFUSION 

of  this  nature  I  have  encountered.  Fortunately,  the 
patient  recovered* 

Haemolysis  may  occur  in  three  ways:  (1)  The  red 
cells  of  the  donor  may  he  destroyed  by  the  patient's 
serum;  (2)  the  red  cells  of  the  recipient  may  be  hoemo- 
lyzed  by  the  donor's  serum;  or  (3)  the  red  cells  of 
both  may  be  destroyed  by  each  other's  serum,  an  even- 
tuality of  the  gi-avest  sort.  Naturally,  if  the  patient's 
serum  is  haemolytic  to  donor's  corpuscles  the  degree  of 
haemolysis  will  depend  entirely  on  two  factors — ^first, 
the  toxicity  of  the  serum,  and,  second,  the  extent  of 
the  transfusion  or  the  number  of  corpuscles  intro- 
duced, because  after  they  have  all  been  destroyed  the 
process  must  cease.  If,  on  the  other  hand,  the  donor's 
serimi  is  injurious  to  the  patient's  cell,  the  degree  of 
haemolysis  depends  solely  on  the  toxicity  of  the  senmi ; 
if  it  is  strong  enough  there  is  no  reason  why  it  should 
not  destroy  every  red  corpuscle  in  the  body.  Natu- 
rally, if  both  sera  are  lytic,  both  the  red  cells  intro- 
duced and  the  host's  cells  are  liable  to  destruction  in 
part  or  in  toto,  according  to  the  lytic  powers  of  the 
sera,  one  of  which  may  be  stronger  than  the  other. 

Thus  the  absolute  necessity  for  preliminary  tests 
must  be  apparent  to  all.  When  blood  transfusion  first 
came  into  vogue  it  was  the  common  thing  to  poke  fun 
at  haemolytic  tests;  many  men  had  done  numerous 
transfusions  without  tests  and  without  the  sign  of 


DANGERS  OF  TRANSFUSION  67 

hemolysis  or  other  trouble,  so  that  the  feehng  arose 
that  its  occurrence  was  a  remote  possibihty  and  there- 
fore one  to  be  ignored.  But  it  was  not  long  before 
cases  of  haemolysis  began  to  make  their  appearance, 
and  with  the  growing  popularity  of  transfusion  they 
became  more  and  more  common,  until  a  number  of 
fatalities  had  occurred  and  a  distinct  change  of  senti- 
ment concerning  the  importance  of  the  complication 
was  noted. 

The  reason  for  this  early  false  security  undoubt- 
edly was  that  the  phenomenon  of  haemolysis  apparently 
does  not  necessarily  take  place  in  unlike  or  unsuitable 
bloods  every  time  they  are  mixed,  the  explanation  for 
this  singular  state  of  affairs  being  unknown.  This  has 
been  proved  by  the  fact  that  not  once  but  many  times 
bloods  have  been  shown  to  be  incompatible  in  test- 
tubes,  but  in  vivo,  in  the  body,  no  trouble  has  followed 
transfusion.  The  trouble  is  that  one  cannot  predict 
the  com*se  of  events  and,  since  the  vast  majority  of 
bloods  that  are  incompatible  in  laboratory  prove  to 
be  so  at  transfusion,  the  safest  course  to  pursue  is  to 
rule  out  all  donors  whose  blood  shows  the  slightest 
antagonistic  tendency  toward  the  patient's  blood,  or 
vice  versa.  If  several  donors  have  undergone  tests  and 
all  of  them  show  incompatibilities  and  no  other  indi- 
viduals are  available  for  further  tests,  or  if  time  is  lack- 
ing in  which  to  carry  out  further  tests  and  if  the  trans- 


08  BLOOD  TRANSFUSION 

fusion  must  be  done,  it  is  customary  to  choose  as  donor 
that  individual  whose  blood  appears  to  be  most  compat- 
ible. In  general  only  a  slight  haemolysis  will  follow  in 
mvo  where  there  has  been  slight  haemolysis  in  test-tubes; 
but  one  can  never  be  sure,  and  the  sense  of  insecurity 
is  most  disturbing.  Furthermore,  even  slight  haemo- 
lysis is  injurious  to  the  kidneys  besides  being  generally 
dangerous,  so  that  I  am  accustomed  to  postpone  trans- 
fusions until  donors  can  be  found  who  are  absolutely 
suitable — unless  delay  is  out  of  the  question  or  there 
absolutely  is  no  possible  way  of  securing  other  donors. 
Never  will  I  forget  the  case  where  a  wife  was  a  hus- 
band's only  possible  source  of  blood,  and  he  needed  it 
badly.  In  spite  of  the  warning  tests,  which,  however, 
indicated  only  slight  incompatibilities,  I  did  the  trans- 
fusion. A  violent  haemolysis  resulted  and  certainly 
undid  all  the  temporary  good  the  new  blood  had  done. 
Fortunately,  the  condition  was  shortlived  and  the 
patient  recovered,  but  his  prostration  while  it  was  go- 
ing on  was  profound,  and  he  certainly  looked  as  if  he 
could  not  survive. 

Where  the  bloods  are  truly  compatible  the  post- 
operative course  of  a  transfusion  is  so  smooth.  There 
is  no  sign  of  a  chill  or  other  discomfort  except  some- 
times a  feeling  of  fulness.  The  temperature  hardly 
rises  above  normal  and  there  is  so  often  that  most  to 
be  desired  feeling  of  well-being  on  the  part  of  the 


DANGERS  OF  TRANSFUSION  69 

patient.  All  the  chills,  the  high  fevers,  the  nausea  and 
vomiting,  restlessness,  et  cetera,  occasionally  met  with 
must  surely  be  the  result  of  incompatibihties,  since 
they  rarely  occur  where  preliminary  tests  have  been 
accurately  done  and  compatible  bloods  used. 

The  phenomenon  of  agglutination,  by  which  is 
understood  the  clumping  of  red  cells,  is  apparently 
much  less  dangerous  to  life  than  haemolysis,  but  is  of 
much  more  frequent  occurrence.  It  has  been  shown 
by  Moss  that  agglutination  frequently  occurs  without 
haemolysis,  but  haemolysis  is  always  associated  with 
agglutination  or  preceded  by  it.  This  knowledge  is 
most  useful  in  carrying  out  appropriate  tests  for 
haemolysis  and  agglutination.^  I  have  never  encoun- 
tered any  trouble  from  it  in  my  own  work  nor  have  I 
ever  seen  any,  although  an  apparently  authentic  case 
of  sudden  death  from  agglutination  occurred  about  one 
year  ago  at  the  Johns  Hopkins  Hospital.  In  this 
instance  the  appropriate  tests  had  been  carried  out, 
but  shortly  after  transfusion  was  begun  sudden  exitus 
took  out,  out  of  a  clear  sky.  The  operator  was  so 
nonplussed  at  the  unexpected  turn  of  events  that  he 
immediately  undertook  a  search  for  the  cause,  during 
the  course  of  which  numerous  blood  smears  were  taken 
which  showed  nothing  but  clumped,  agglutinated  red 
cells,  the  clumps  being  of  all  sizes.    Evidently  the  two 

^  See  Appendix. 


70  BLOOD  TRANSFUSION 

bloods  had  been  so  markedly  agglutinative  toward  each 
other  that  practically  all  the  cells  became  involved  and 
multiple  emboli  promptly  occurred,  with  the  resultant 
fatal  issue.  The  assumption  is  that  an  error  in  technic 
was  responsible. 

Besides  the  above  case  a  few  others  have  been  re- 
ported by  Ottenberg  and  Kaliski  and  others,  some  of 
which  were  fatal  while  some  were  not.  In  a  very  few, 
the  patients  presented  warning  signs  sufficiently  early 
in  the  course  of  the  transfusion  for  it  to  be  discontinued. 
But  the  accidents  resulting  from  this  cause  are  few  and 
far  between.  I  make  it  a  rule  to  use  only  donors  whose 
blood  neither  hsemolizes  nor  agglutinates  either  way 
with  the  patient's — whenever  possible,  even  going  to 
the  length  of  having  more  donors  tested  out,  if  they 
are  available  and  there  is  enough  time,  when  even 
slight  agglutination  is  noted.  But  when  additional 
donors  are  not  available  or  time  is  short,  I  use  without 
hesitation  that  donor  in  whose  blood  there  is  least  to  be 
feared  from  agglutination,  and  I  must  confess  that  I 
have  never  seen  the  slightest  trouble  arise  either  during 
or  after  transfusion  as  a  consequence. 

The  crux  of  the  matter  then,  as  far  as  agglutina- 
tion goes,  would  seem  to  be  that  sudden  death  may 
be  expected  or  may  occur  when  two  bloods  are  mixed 
which  are  actively  agglutinative,  but  in  the  lesser 
grades  any  clumping  that  may  take  place  simply 


DANGERS  OF  TRANSFUSION  71 

amounts  to  making  useless  the  cells  affected,  for 
whenever  red  cells  clump  they  are  necessarily  injured 
and  their  period  of  usefulness  is  over.  Therefore,  if, 
for  example,  one  were  to  introduce  500  c.c.  of  blood 
into  a  circulation  and  the  recipient's  plasma  should 
cause  agglutination  of  this  blood,  little  clumps  of  all 
the  fresh  blood  would  form  with  the  result  that  the 
blood  might  as  well  not  have  been  introduced,  because 
at  one  fell  blow  the  cells  are  all  rendered  useless — 
quite  aside  from  the  harm  they  might  do  the  host 
by  plugging  up  capillaries,  or  kidney  tubules,  or  by 
making  the  host  absorb  the  products  of  their  cell  de- 
struction. And  if  in  addition  the  donor's  blood  should 
be  agglutinative  to  the  recipient's  blood  not  only  would 
the  500  c.c.  introduced  be  put  out  of  action,  but  a 
considerable  amount  of  the  host's  blood  might  suffer 
the  same  fate ;  so  that  instead  of  helping  matters  and 
relieving  anaemia,  a\  still  further  anaemia  might  be 
caused.  In  short,  even  if  no  actual  disaster  does  fol- 
low agglutination,  it  is  pure  waste  to  transfuse  blood 
where  this  phenomenon  is  liable  to  occur,  because  the 
introduced  blood  is  put  out  of  commission  immediately, 
and  therefore  cannot  serve  the  purpose  for  which  it 
was  intended.  Even  if  only  part  of  it  is  rendered  use- 
less, the  waste  is  considerable  and  this,  taken  in  con- 
junction with  the  danger,  is  quite  sufficient  to  rule  out 
blood  liable  to  give  rise  to  the  phenomenon. 

It  must  be  granted,  then,  that  the  phenomena  of 


n  BLOOD  TR.VNSFUSION 

hemolysis  and  agglutination  are  real  dangers  in  blood 
transfusion  and  that  every  possible  effort  should  be 
made  to  eliminate  them  as  complications,  for  which 
purpose  certain  tests  have  been  elaborated  whereby 
their  occurrence  may  be  predicted  in  advance.  Unfor- 
tunately these  tests  are  rather  delicate  and  require 
skilled  laboratory  workers  and  facilities  not  found  in 
the  ordinary  hospital.  And,  in  addition,  if  they  are 
to  be  accurate  they  require  not  less  than  one  and  one- 
half  hours'  time  (frequently  two  to  two  and  one-half 
hours)  after  blood  specimens  have  been  secured  from 
all  parties  concerned.  Certain  tests  have  been  sug- 
gested which  consume  less  time,  but  experience  has 
proved  them  to  be  correspondingly  less  accurate  than 
those  taking  longer  to  do;  so  that  advantage  cannot 
be  taken  of  tests  in  the  grave  emergencies,  although 
I  have  frequently  been  able  to  have  them  done  in  cer- 
tain of  these  cases  by  having  blood  specimens  taken 
the  moment  transfusion  is  considered.  But  it  is  always 
hazardous  to  delay  and  in  one  rather  recent  case  of 
post-operative  hemorrhage  and  shock  the  wait  almost 
proved  disastrous.  Decision  in  the  matter  simply 
amounts  to  determining  in  which  direction  lays  the 
greatest  risk — letting  the  patient  wait  a  couple  of 
hours  for  the  result  of  the  tests  and  run  the  chance 
of  dying  in  the  meantime,  or  doing  the  transfusion  and 
letting  the  patient  take  the  risk  of  receiving  an  incom- 


DANGERS  OF  TRANSFUSION  73 

patible  blood.  To  my  mind  the  latter  is  far  the  lesser 
risk  of  the  two  because,  according  to  the  statistics  cited 
at  the  beginning  of  this  chapter,  out  of  800  transfusions, 
a  great  number  of  which  were  done  without  preliminary 
tests,  haemolysis  occurred  in  only  about  2  per  cent,  of 
the  cases.  Its  true  incidence  is  probably  nearer  4  per 
cent.,  but  even  so  my  feeling  is  that  certain  patients  will 
have  a  much  better  chance  for  life  by  taking  this  risk 
than  by  waiting  for  the  tests  to  be  carried  out.  And  it 
nmst  always  be  remembered  that  even  when  haemol- 
ysis does  occur  the  majority  of  the  cases  recover. 
Out  of  six  recent  emergencies  where  testing  was 
entirely  out  of  the  question,  no  case  of  haemolysis  or 
agglutination  occurred,  although  one  patient  did  suf- 
fer a  most  violent  chill  about  twenty  minutes  after 
the  transfusion.  A  certain  incompatibility  must  have 
been  present,  but  it  was  not  severe  enough  to  cause 
haemolysis  or  affect  the  course  of  the  patient's  illness.^ 
However,  in  those  cases  where  tests  are  not  to  be 
done  or  laboratory  workers  are  not  available,  it  is 
wise  to  secure  as  donor  the  closest  absolute  blood  rela- 
tive obtainable.  The  reason  for  this  is  that  Moss  has 
shown  that,  as  regards  haemolysis  and  agglutination,  all 
human  bloods  fall  into  four  permanent,  hereditary, 

^  This  was  a  sodium  citrate  transfusion  and  the  citrate 
may  have  caused  the  chill.    See  citrate  method  of  transfusion. 


74  BLOOD  TRANSFUSION 

and  sharply  defined  groups  and  that  to  a  great  ex- 
tent blood  relatives  come  in  similar  groups.  Those 
bloods  which  fall  in  the  same  group  neither  haemolize 
nor  agglutinate  each  other,  so  the  wisdom  of  choosing 
blood  relatives  as  donors  in  emergencies  is  apparent. 
This,  of  course,  is  not  an  absolute  rule;  I  have  seen 
the  most  violent  incompatibilities  between  brother's 
and  sister's  bloods,  but  so  nearly  the  rule  is  it  that 
where  relatives  and  non-relatives  are  tested  out,  the 
report  frequently  comes  back  that,  while  one  or  two 
of  the  non-relatives  might  be  perfectly  good  donors, 
there  is  just  the  faintest  suggestion  of  agglutination  be- 
tween their  bloods  and  the  patient's,  but  no  sign  of  it 
between  the  relative's  blood  and  the  patient's. 

But  there  is  still  another  factor  of  safety  that  gives 
a  certain  amount  of  comfort  and  security  when  emer- 
gency transfusions  become  necessary  and  that  is  the 
percentage  study  that  has  been  worked  out  for  the 
four  groups  into  which  all  bloods  fall.  Approximately 
it  is  as  follows : 

Group  I —  2  per  cent,  of  all  bloods. 

Group  II — 4iO  per  cent,  of  all  bloods. 

Group  III — 15  per  cent,  of  all  bloods. 

Group  IV — 4<3  per  cent,  of  all  bloocls. 

It  will  thus  be  seen  that  about  83  per  cent,  of  all 
bloods  fall  into  two  groups  and  the  chances  are  there- 
fore very  good  that  an  untested  donor  and  recipient  will 


DANGERS  OF  TRANSFUSION  75 

fall  in  one  of  them.  Whether  they  will  or  will  not,  or 
whether  they  will  be  in  the  same  one  of  the  common 
groups  is,  of  com'se,  pm*ely  a  matter  of  chance.  But 
this  probably  accounts  for  the  comparative  freedom 
from  haemolysis  and  agglutination  encountered  in 
untested  transfusions;  and  it  was  this  unknown  state 
of  affairs  that  gave  rise  to  the  early  skepticism  regard- 
ing the  occurrence  of  the  phenomena  and  the  necessity 
for  preliminary  tests  to  avoid  them.  That  it  is  a 
security  upon  which  too  much  reliance  must  not  be 
placed  has  been  amply  and  repeatedlj^  demonstrated. 
The  actual  tests  will  be  appended. 

REFERENCES 

Bernheim,  B.  M. :  "  Hasmolysis  Following  Transfusion  of 
Blood ;  A  Study."    The  Lancet-Clinic,  March  6,  1915. 

Brem,  W.  V. :  "  Blood  Transfusion  with  Special  Reference 
to  Group  Tests."  J.  A.  M.  A.,  1916,  Ixvii. 

Cherry,  T.  H.,  and  Langrock,  E.  G. :  "  The  Relation  of  Hae- 
molysis in  the  Transfusion  of  Babies  with  the  Mothers 
as  Donors."  J.  A.  M.  A.,  February  26,  1916,  vol.  Ixvi. 

Lindeman,  E. :  "  Reactions  Following  Blood  Transfusion  by 
the  Syringe  Cannula  System."  J.  A.  M.  A.,  February 
26,  1916,  vol.  Ixvi,  pp.  624,  626. 

McClure,  Roy  D.,  M.D.,  F.A.C.S.,  and  Dunn,  George  Robert, 
M.D. :  "  Transfusion  of  Blood.  History,  Methods,  Dan- 
gers, Preliminary  Tests,  Present  Status."  Report  of 
One  Hundred  and  Fifty  Transfusions.  From  the  Bul- 
letin of  the  Johns  Hopkins  Hospital,  vol.  xxviii,  No. 
313,  March,  1917. 


7«  BLOOD  TRANSFUSION 

Minot,  George  R. :  "  Methods  for  Testing  Donors  for  Trans- 
fusion of  Blood  and  Consideration  of  Factors  Influenc- 
ing Agglutination  and  Haemolysis."  Boston  Med.  and 
Surg.  Journ.,  May  11,  1916. 

Moss,  W.  L. :  "  Studies  on  Iso-agglutinins  and  Iso-haemo- 
lysins."  Johns  Hopkins  Hospital  Bidletvn,  1910,  xxi,  63. 

Ottenberg,  R.,  and  Kaliski,  D.  J. :  "Accidents  in  Transfu- 
sion. Their  Prevention  by  Preliminary  Examination; 
Based  on  an  experience  of  128  Transfusions."  J.  A. 
M.  A.,  December  13,  1913. 

Ottenberg,  R. :  "1.  Transfusion  and  the  Question  of  Intra- 
vascular Agglutination."  Journal  of  Exp.  Med.,  vol. 
xiii.  No.  4,  1911. 

Ottenberg,  Kaliski,  and  Friedman :  "  Haemolysis."  Journal 
Med.  Research,  1913,  xxviii,  l^l. 


CHAPTER  VI 

SELECTION  OF  DONOR  FOR  TRANSFUSION.  DAN- 
GERS TO  DONOR.  TREATMENT  OF  DONOR 
AFTER  TRANSFUSION 

The  term  donor  is  used  to  designate  the  individual 
who  supplies  the  blood  in  a  transfusion,  and  the  term 
recipient  is  used  to  designate  the  patient.  The  recipi- 
ent is,  of  course,  constant,  but  the  donor  is  by  no 
means  so,  except,  perhaps,  in  those  few  instances  where 
only  one  person  is  available  as  a  blood  supply  and 
conditions  are  such  that  he  must  be  used,  suitable  or 
not — fortunately  a  rare  occurrence  Human  nature 
is  all-enveloping  and  nearly  always  volunteers  are 
forthcoming. 

It  was  formerly  considered  sufficient  for  the  pur- 
poses of  transfusion  to  get  a  big  well-built  man  to  act 
as  donor  because  of  the  severity  of  the  ordeal  he  had  to 
undergo  and  his  ability  to  withstand  blood  loss  with 
equanimity,  but  with  the  advent  of  definite  knowledge 
concerning  hsemolysis  and  agglutination,  there  arose 
the  custom  of  preliminary  blood  tests  which  iniled  out 
many  apparently  good  prospective  donors.  It  is  still 
advisable  to  have  a  strong  young  person  as  donor,  but 
between  a  well-built,  up-standing  individual  whose 
blood  does  not  mix  with  the  patient's  and  an  elderly, 

77 


78  BLOOD  TRANSFUSION 

anaemic-looking  nervous  person  whose  blood  does  mix 
there  can  be  no  choice — experience  has  taught  the  abso- 
lute necessity  of  using  bloods  of  the  same  group  if 
success  is  to  be  attained. 

But  there  are  other  features  besides  blood  tests  to 
be  considered  in  selecting  donors,  which  may  seem 
trivial  to  many,  but  are  not  at  all  so  to  those  actually 
concerned  as  parties  to  the  transfusion.  For  instance, 
the  father  of  a  large  family  might  well  be  passed  over 
in  favor  of  his  son  or  even  a  volunteer  friend,  other 
things  such  as  blood  test  requirements  being  equal,  in 
acting  as  donor  to  his  wife  or  child.  His  anxieties  are 
a  sufficient  burden  and  personal  inconvenience  can 
only  make  matters  worse — and,  besides,  as  bread-win- 
ner, his  activity  might  be  crippled  at  a  time  when  it  is 
most  needed.  For  the  same  reason  the  sister  might 
at  times  be  chosen  instead  of  the  brother. 

Age  plays  but  a  slight  role  in  this  question.  Natu- 
rally the  very  young  and  the  very  old  are  eliminated, 
but  I  have  used  a  boy  of  seventeen  as  a  donor  for  his 
mother,  and  a  man  of  nearly  sixty  as  donor  tc  his  son, 
without  untoward  consequences.  One  can  hardly 
escape  the  conviction,  though,  that  if  possible  only 
adults  between  twenty  and  fifty  should  be  used.  Blood 
loss  can  hardly  be  beneficial  to  a  boy  or  girl  still  in  the 
growing  period,  and  it  is  quite  conceivable  that  even 
temporary  weakness  due  to  this  cause  might  be  quite 
harmful  to  either  young  or  old. 


i 


SELECTION  OF  DONOR  FOR  TRANSFUSION      79 

Certain  people  are  eliminated  as  donors  by  their 
temperament,  though  this  was  much  more  common  in 
the  days  of  direct  transfusion  than  it  is  at  present.  The 
anxious  parent  is  not  the  best  donor  and  a  hysterical 
daughter  is  hardly  to  be  considered.  By  the  same 
token,  an  unwilling  donor  is  an  abomination;  every- 
thing hurts  him,  he  has  all  sorts  of  imusual  symptoms 
and  I  have  even  had  one  to  actually  stop  the  pro- 
cedure after  giving  but  a  small  fraction  of  the  amount 
desired. 

If  a  du'ect  transfusion  is  to  be  done,  or  even  in  the 
case  of  an  indirect  transfusion,  the  nature  of  the 
donor's  employment  deserves  consideration  as  well 
as  the  question  of  his  being  right-  or  left-handed. 
Obviously  when  a  person  is  right-handed  his  left  arm 
should  be  used,  if  possible,  and  when  left-handed  his 
right  arm  is  preferable  and,  in  the  case  of  two  avail- 
able donors — if  one  man's  work  is  of  a  highly  skilled, 
specialized  natm-e,  which  depends  upon  his  perfect 
wrist  or  elbow,  and  the  other  man's  work  is  unskilled, 
the  latter  should  always  be  chosen. 

In  certain  respects  a  relative,  a  near  relative,  is 
preferable  to  a  non-relative.  The  bloods  are  more 
liable  to  be  satisfactory,  but  more  important  than  this 
is  the  fact  that  one  feels  more  justified  in  taking  large 
quantities  from  a  relative  who  is  usually  willing  to 
make  a  sacrifice,  even  to  the  point  of  several  days' 
inconvenience. 


80  BLOOD  TRANSFUSION 

This  naturally  leads  up  to  the  question  of  paid 
donors — a  latter  day  development  in  this  work  which 
has  been  necessitated  by  a  realization  upon  the  part  of 
medical  men  of  the  wide  therapeutic  usefulness  of 
blood,  provided  it  could  be  obtained  in  quantities  de- 
sired without  incommoding  relatives  other  than  in  a 
financial  way.  Those  in  small  communities  hardly 
have  occasion  to  consider  this  matter,  since  transfu- 
sions are  of  rather  infrequent  occurrence  and  donors 
can  always  be  had  from  friends  or  relatives.  But  in 
the  large  cities,  the  paid  donor  is  playing  a  decided 
part  in  the  development  of  transfusion  work.  His 
remuneration  is  by  no  means  excessive — on  the  con- 
trary, it  is  usually  small,  but,  like  every  other  com- 
modity, demand  regulates  the  supply  and  its  cost. 

The  custom  of  advertising  for  men  to  give  up  part 
of  their  blood  for  pay  originated  in  New  York  where 
it  was  impossible  to  obtain  suitable  donors  in  sufficient 
numbers.  It  must  be  remembered  that  the  haemolytic 
and  Wassermann  tests  eliminate  numbers  of  other- 
wise good  donors,  so  that  it  is  desirable  to  test  not 
less  than  four  or  five  individuals  every  time  a  trans- 
fusion is  in  prospect.  But  advertising  for  men  is 
not  an  ideal  method  of  procuring  them,  and  it  has 
been  found  practicable  to  obtain  them  almost  at  a 
moment's  notice  from  the  various  lodging  houses  fre- 
quented by  the  idle  in  all  large  cities.    This  method 


SELECTION  OF  DONOR  FOR  TRANSFUSION      81 

is  preferable  to  advertising — because  it  makes  possible 
the  securing  of  donors  for  emergency  transfusion,  an 
impossibility,  naturally,  through  the  advertising 
medium.  In  addition  to  this,  there  is  the  further 
advantage  of  familiarity  upon  the  part  of  the  attend- 
ants and  certain  habitues  of  the  lodging  house  with 
the  procedure  of  transfusion,  thereby  rendering  it  easy 
to  secure  men  who,  under  other  circumstances,  might 
be  timid  about  sacrificing  part  of  their  blood  even  for 
large  sums  of  money.  As  a  result  of  this  custom,  there 
has  arisen  a  small  group  of  so-called  professional 
donors — men  who  have  undergone  several  transfusions 
and  are  content  to  give  their  blood  at  rather  frequent 
intervals.  I  have  known  men  who  have  submitted  to 
the  procedure  half  a  dozen  times  within  two  years, 
apparently  unharmed,  but  since  continued  blood  losses 
must  surely  put  a  strain  upon  the  blood-forming  pro- 
cesses of  the  body  which  in  time  might  react  harmfully 
upon  the  individual,  I  think  this  custom  is  not  to  be 
encouraged.  It  is  an  easy  way  to  make  money  and  I 
have  heard  that  in  Xew  York  there  are  professionals 
who  have  given  blood  more  than  a  dozen  times. 

With  regard  to  the  advisability  of  utilizing  paid 
donors,  I  can  only  say  that  in  my  experience  they  have 
been  more  desirable  than  relatives,  because  the  psychic 
element  of  anxiety  for  the  welfare  of  the  patient  is 
totally  absent,  and,  except  for  a  slight  timidity  for 


82  BLOOD  TRANSFUSION 

their  own  safety  (and  tliis  is  seldom  seen),  they  make 
brave,  even  sympatlietic,  donors.  jSIost  of  them  are 
young,  decent,  self-respecting  men,  temporarily  out 
of  employment,  who  have  just  enough  of  the  "  sport- 
ing "  element  in  their  make-up  to  be  interested  in  what 
is  taking  place  and  to  be  desirous  of  doing  all  in  their 
power  to  bring  about  a  success.  It  is  a  common  occur- 
rence to  have  them  suggest  that  no  thought  be  given 
them  in  determining  the  amount  of  blood  to  be  taken, 
but  I  am  always  extremely  careful  7iot  to  take  too 
much,  and  prefer  to  take  too  little  rather  than  inca- 
pacitate or  weaken  a  man  who  depends  uj^on  his  physi- 
cal work  for  his  support.  In  my  experience,  the 
amount  of  blood  taken  from  these  donors  has  always 
sufficed.  When  I  have  thought  that  I  might  need 
more  than  one  man  could  safely  furnish,  I  have  held 
ready  a  second  one  as  a  reserve  supply. 

Actual  dangers  to  donors  are  neither  numerous 
nor  serious.  I  have  never  lost  a  donor  nor  have  I  ever 
heard  of  a  person  losing  his  life  by  giving  blood  in  a 
transfusion,  though  I  did  have  one  willing,  unpaid 
donor  remain  in  a  weakened  state  of  physical  relaxa- 
tion for  several  months  following  an  emergency  trans- 
fusion where  time  to  do  hasmolytic  tests  was  lacking 
and  the  donor's  blood,  as  afterwards  was  discovered, 
destroyed  the  patient's  cells  in  such  numbers  as  to 
cause  the  only  fatal  case  of  haemolysis  in  my  series. 


SELECTION  OF  DONOR  FOR  TRANSFUSION      83 

The  donor  was  a  life-long  friend  of  the  recipient  and 
her  mental  anguish  possibly  played  a  part  in  her  fail- 
ure to  recover  proni2)th\  She  did  finally  regain  her 
health,  and  has  remained  well  since. 

In  the  days  of  direct  transfusion,  there  was  more 
danger  to  a  donor  than  is  the  case  at  present  because 
of  the  necessity  of  dissecting  out  the  radial  artery  and 
the  possibility  of  infecting  the  arm  through  faulty 
technic.  When  the  recipient  was  suffering  from  some 
communicable  disease,  such  as  a  pyogenic  septicaemia 
or  typhoid  infection,  the  danger  was  increased,  but  I, 
in  company  with  many  other  sm'geons,  have  been  able 
to  carry  out  a  nmnber  of  such  transfusions,  without 
infecting  the  donor,  by  means  of  a  technic  far  more 
elaborate  and  painstaking  than  ordinarily  required. 

With  the  introduction  of  the  indirect  method  of 
transfusion  all  danger  to  the  donor  has  disappeared, 
except  perhaps  that  of  actual  blood  loss,  but  since 
the  quantity  is  rarely  over  750  c.c.  or  1000  c.c.  there 
is  little  risk.  A  certain  amount  of  nausea  and  occa- 
sional vomiting  may  be  seen  dm*ing  the  course  of  blood 
removal,  but  if  one  is  careful  not  to  have  the  flow  too 
fast  this  can  always  be  avoided.  It  is  wise  to  direct  the 
donor's  attention  from  the  depletion  and  to  distract  him 
by  means  of  conversation  and  the  feeding  of  bits  of 
cracked  ice.  I  never  give  a  preliminarj^  dose  of  mor- 
pliine  to  a  donor,  though  this  custom  is  practised  to 


84  BLOOD  TRANSFUSION 

a  certain  extent  elsewhere.  Morphia  tends  to  lower 
the  blood-pressure  and  in  my  experience  is  entirely 
unnecessary  for  reassuring  purposes.  If  signs  of 
nausea  appear  I  try  to  reassure  the  donor  that  he  will 
not  be  injured  in  the  slightest,  and  at  the  same  time 
retard  the  outflow  of  blood.  If  the  signs  progress, 
if  he  turns  pale  and  begins  to  perspire,  the  head  of 
the  table  is  lowered  a  little  and  he  is  given  some 
aromatic  spirits  of  ammonia  to  inhale;  if  this  fails 
to  help  and  vomiting  seems  imminent,  I  immediateh' 
stop  the  operation  until  he  recovers.  I  have  had  only 
one  case  of  this  sort  in  the  last  three  years  and  in  that 
instance  the  nausea  came  so  suddenly  that  it  could  not 
be  avoided.  Sufficient  blood  had  already  been  taken, 
so  the  needle  was  removed  and  a  prompt  recovery 
ensued. 

In  some  clinics  the  custom  is  followed  of  putting 
into  the  donor's  vein  an  amount  of  salt  solution  equal 
to  the  volume  of  blood  removed,  but  I  have  not  found 
this  necessary  or  advisable,  since  it  is  my  custom  never 
to  take  more  than  800  c.c.  of  blood  from  any  one,  and 
even  this  safe  amount  is  taken  only  from  those  well 
able  to  lose  it.  The  introduction  of  fluids  to  make  up 
the  deficiency,  though,  is  advisable,  and  I  have  a  hot 
cup  of  cocoa  or  milk  given  immediately  upon  cessation 
of  the  operation  and  then  instruct  the  donor  to  drink 
freely  of  water,  tea,  coffee,  cocoa  or  milk  during  the 
next  three  or  four  days.    They  all  follow  these  instruc- 


SELECTION  OF  DONOR  FOR  TRANSFUSION      85 

tions  because  of  the  thirst  that  supervenes  upon  any 
appreciable  blood  loss. 

More  important  than  making  up  the  plasma  loss 
is  that  of  retrieving  the  cellular  content  of  the  blood, 
and  to  that  end  I  advise  rest  for  a  day,  not  necessarily 
in  bed,  plenty  of  fresh  air  and  nourishing  food.  I 
have  never  given  tonics  because  statistics  show  that  the 
healthy  man  or  woman  will  make  up  the  blood  lost 
during  a  transfusion  within  four  or  five  days. 

If  small  amounts  of  blood  are  removed — 250  to 
300  c.c.^ — there  is  no  reason  why  the  same  donor  should 
not  be  used  two  or  three  times  in  succession  at  intervals 
of  several  days ;  but  if  larger  amounts  have  been  taken 
it  is  unwise  to  use  him  again  under  two  weeks  except 
in  critical  circumstances.  I  have  never  used  the  same 
donor  more  than  three  times.  Several  times,  though,  I 
have  taken  blood  from  donors  who  had  been  used  by 
other  operators  five  and  six  times ;  all  of  them  seemed 
to  be  in  robust  health  and  had  not  "  served  "  recently ; 
and  their  familiarity  with  the  procedure  made  them  a 
great  comfort.  One  of  them  criticised  my  technic 
throughout  the  whole  operation,  and,  I  must  admit, 
to  my  detriment ;  but  since  everything  went  off  accord- 
ing to  schedule  and  he  suffered  no  inconvenience,  I 
think  he  was  reconciled  to  my  shortcomings. 

It  has  often  been  noticed,  but  not  explained,  that 
in  cases  where  multiple  transfusions  have  been  done 


86  BLOOD  TRANSFUSION 

on  the  same  patient  and  different  donors  have  been 
used,  it  has  appeared  that  one  man's  blood  was  produc- 
tive of  more  benefit  than  another's,  although  all  donors 
had  been  carefully  tested,  were  in  the  same  group, 
and  the  same  amount  of  blood  was  used  each  time 
with  the  same  technic.  In  one  of  my  cases  where  six 
transfusions  were  carried  out,  this  fact  was  so  striking 
that  I  used  the  first  donor  a  second  time  and  demon- 
strated the  greater  efficiency  of  his  blood  as  compared 
to  that  of  the  others.  Whether  this  is  due  to  the 
donor's  blood  or  to  different  phases  of  the  patient's 
condition  is  not  clear,  but  it  is  a-  feature  worth  keeping 
in  mind  whenever  multiple  transfusions  are  in  order. 
Perhaps  later  serological  studies  will  shed  more  light 
on  the  phenomenon. 

REFERENCES 
Morawitz,  P. :  "  Einige  neuere  Auschauungen  iiber  Blutre- 

generation."   Ergebn.  d.  imm.  Med.  n.  Kinderh,  Berlin, 

1913,  xi,  277-323. 
Schmidt,  P. :  "  Ein  Beitrag  zur  Frage  der  Blutregeneration." 

Munch,  med.  Wochnschr.,  1903,  1,  549-553. 


CHAPTER  VII 
METHODS  OF  TRANSFUSION.    TECHNIC 

The  transfusion  of  blood  may  be  accomplished 
either  by  having  the  blood  flow  from  the  vessels  of 
one  individual  directly  into  the  vessels  of  another,  this 
procedure  being  known  as  direct  transfusion,  or  the 
blood  may  be  removed  from  one  person  and  injected 
or  allowed  to  flow  into  the  vessels  of  another,  this  pro- 
cedure being  known  as  indirect  transfusion. 

The  direct  method  was  first  to  become  popular 
because  of  Crile's  epoch-making  work  on  blood  trans- 
fusion some  ten  or  twelve  years  ago.  He  perfected  a 
little  silver  tube  and  evolved  a  suitable  technic  whereby 
an  artery  of  one  person  could  be  united  with  a  vein 
of  another  with  such  accuracy  that  blood  would  flow 
without  hindrance  directly  from  one  to  the  other  and 
for  as  long  a  time  as  was  necessary  or  desirable.  This 
was  the  real  beginning  of  transfusion  as  we  now  know 
it.  Hitherto,  it  had  been  practically  impossible  to 
transfer  blood  with  any  degree  of  accuracy  or  cer- 
tainty by  any  of  the  methods  extant,  so  that  when 
Crile's  tube  and  technic  made  their  appearance  a  long- 
felt  need  was  fulfilled  and  it  was  not  long  before  re- 
ports of  transfusions  began  to  appear  with  increasing 
frequency. 

87 


88  BLOOD  TRANSFUSION 

Thus  it  came  about  that  many  workers  centred 
their  attention  on  this  fascinating  subject,  with  the 
result  that  it  soon  became  appai'ent  that  Crile's  tube 
had  many  decided  hmitations,  chief  among  which  was 
the  not  inconsiderable  amount  of  special  training  re- 
quired before  one  could  really  use  it  with  uniform 
success.  ^lany  modifications  of  the  tube  were  sug- 
gested, all  with  the  view  to  simplification,  and  sev- 
eral decided  improvements  were  suggested,  but  fm*- 
ther  work  demonstrated  the  fact  that  a  tube  of  an 
entirely  different  constructive  principle  would  answer 
the  purpose  just  as  well  and  require  far  less  special 
training  for  its  employment.  Crile's  tube  gradually 
fell  into  disuse  and  the  newer  instruments  took  its 
place,  all,  however,  being  adapted  only  for  direct 
transfusion.  But  there  were  always  two  serious  draw- 
backs to  the  direct  method — the  amount  of  blood 
transfused  could  not  be  accurately  measured  and  an 
incision  in  both  donor  and  recipient  was  required  each 
time  it  was  done,  the  radial  artery  of  the  donor  being 
sacrificed  in  every  instance.  Serious  as  these  diffi- 
culties were,  the  need  for  a  change  did  not  become 
really  urgent  until  the  field  for  transfusion  began 
to  widen  to  such  extent  that  its  usefulness  seemed 
likely  to  be  greatly  curtailed  unless  the  blood  amount 
could  be  accurately  measured  and  donors  could  be 
used  without  being  subjected  to  an  operation,  with  its 
consequent  disability.    Then  it  was  that  indirect  trans- 


METHODS  OF  TRANSFUSION  89 

fusion,  which  had  been  tried  and  discarded  years  ago, 
again  made  its  appearance  in  the  form  known  best  as 
the  needle  and  syringe  method  of  Lindeman,  whereby 
blood  was  withdrawn  by  means  of  a  needle  inserted 
into  the  donor's  vein,  and  injected  in  a  similar  manner 
into  a  vein  of  the  recipient,  successive  syringes  being 
emploj^ed.  This  method  was  cumbersome  and  pre- 
sented other  deficiencies,  but  the  need  for  it  was  great 
and  its  use  slowly  and  surely  spread.  Later  on  modi- 
fications made  their  appearance  and  from  it  have 
developed  several  methods  whereby  blood  can  be  indi- 
rectly transfused  with  far  greater  ease,  rapidity  and 
accuracy  than  ever  before,  as  a  consequence  of  which 
the  death  knell  of  direct  transfusion  has  been  sounded. 
Occasions  will  undoubtedly  present  themselves  when 
the  direct  method  should  be  used — but  these  will  be- 
come constantly  rarer. 

From  the  foregoing  sketch,  one  might  conclude 
that  the  last  word  in  transfusion  methods  has  been 
said — and  so  it  has,  perhaps,  so  far  as  the  whole,  un- 
treated blood  is  concerned,  but  it  is  by  no  means  cer- 
tain that  the  future  will  deal  with  blood  in  its  natural 
state.  The  difficult}^  is  that  blood  clots  with  great 
rapidity,  which  makes  it  difficult  to  work  with,  and 
limits  its  possible  usefulness,  so  that  there  has  come 
about  the  need  for  some  means  of  preventing  coagula- 
tion or  at  least  delaj^ing  it.  To  this  end  anticoagulants, 
long  known  and  made  use  of  for  experimental  purposes. 


90  BLOOD  TRANSFUSION 

have  assumed  practical  clinical  importance.  It  is  un- 
necessary here  to  detail  the  work  on  the  substance 
known  as  hirudin  further  than  to  note  its  failure  as 
far  as  humans  are  concerned.  More  to  the  point  is 
the  consideration  of  sodium  citrate  which  in  the  hands 
of  Lewisohn  of  Xew  York  has  given  practical  results 
of  most  promising  character.  By  using  this  drug  in 
a  dilution  of  two-tenths  of  one  per  cent.  (0.2  per  cent. ) 
Lewisohn  demonstrated  that  blood  could  be  kept  un- 
coagulated  for  hours,  over  forty-eight  hours,  and  at 
any  time  during  that  period  it  was  suitable  for  trans- 
fusion.^ Other  workers  have  confirmed  Lewisohn's 
results  and  the  method,  while  still  in  the  probationary 
period,  is  constantly  making  new  friends.  That  it 
will  eventually  supercede  all  other  methods,  perhaps 
in  a  modified  form,  I  have  no  doubt. 

Thus  we  really  have  three  methods  of  blood  trans- 
fusion, the  direct,  the  indirect  whole  blood  and  the 
indirect  anticoagulation  method  and,  since  there  are 
several  ways  of  accomplishing  each,  I  will  give  in 
detail  several  of  the  best  methods  under  each  heading. 

DIRECT  TRANSFUSION 
Chile's  Method 

*'  The  vessels  to  be  anastomosed  (radial  artery  of 
donor  and  an  arm  vein  of  the  recipient)  are  exposed, 

^  Personally,  I  feel  that  it  is  unwise  to  use  blood  that  has 
been  out  of  the  body  longer  than  twelve  hours. 


METHODS  OF  TRANSFUSION 


91 


and,  after  selection  of  a  cannula  (Fig.  1)  of  size 
suitable  to  the  size  of  the  vessel,  the  end  of  the  vein  is 
pulled  through  the  handle  end  of  the  tube 
by  means  of  a  single  fine  suture  inserted  in 
its  edge  (Fig.  2) ,  the  needle  being  left  on  the 
suture  and  passed  through  the  cannula  ahead 
of  the  vein.     The  handle  of  the  cannula  is 

.  •  «   1  FiG.l.— Crile 

then  tightly  seized  by  a  pair  of  haemostats,      cannula. 
three  mosquito  haemostats  are  snapped  at  equidistant 
points  on  the  end  of  the  vein,  taking  care  not  to  have 


Fig.  2. — Drawing  vein  through  cannula. 

the  tips  extend  up  into  the  lumen  more  than  is  neces- 
sary to  get  a  firm  hold.  The  end  of  the  vein  is  then 
cuffed  back  over  the  cannula  by  gentle  simultaneous 


9£ 


BLOOD  TRANSFUSION 


traction  on  the  three  hasmostats  (Fig.  3)  and  tied 
firmly  in  place  with  a  fine  linen  thread  in  the  groove 
nearest  the  handle  ( Fig.  4 ) .  The  cuffed  part  is  next 
covered  with  sterile  vaseline,  being  careful  not  to  get 
any  into  the  open  end.     This  facilitates  slipping  the 


Flo.  3.^CuflSng  vein  back 
over  the  cannula. 


Fia.  4. — Vein  cuffed  and  tied  in  groove 
nearest  handle  of  the  cannula.  Artery 
grasped  by  three  mosquito  clamps. 


artery  over  the  cuff.  The  haemostats  are  removed 
from  the  full  edge  and  the  artery  may  then  be  put 
in  place. 

"  Owing  to  the  elasticity  of  the  arterial  wall,  it 
usually  shrinks  (contracts)  considerably  when  the 
pressure  from  within  is  removed,  as  it  is  at  the  free 


METHODS  OF  TRANSFUSION  93 

end.  To  obviate  this  it  may  be  necessary  to  dilate  the 
end  very  gently  by  inserting  the  closed  jaws  of  a  mos- 
quito clamp  covered  with  vaseline  and  opening  them 
for  a  short  distance.  The  three  hsemostats  are  applied 
to  the  edges,  just  as  with  the  vein,  and  the  artery  is 
gently  drawn  over  the  cuffed  vein  on  the  cannula  and 
tied  in  place  with  another  fine  linen  suture  applied  in 
the  remaining  groove  ( Fig.  5 ) .  The  mosquito  hsemo- 
stats are  removed.  The  process  is  then  completed. 
After  the  transfusion  the  cannula  is  removed,  both 
artery  and  vein  are  ligated  and  the  y 
wounds  are  sutured. 

"  In  making  a  cannula  anastomosis,     fig.  5 —Artery 

slipped    over    can- 

experience  will  show  what  size  cannula  rhi^second  gro1)ve'! 

.  •       1  1        rt  •  -1  *         1  Anastomosis    com- 

is  suitable  for  given  vessels.  As  large  p^'^^e. 
a  size  should  be  used  as  possible,  without  injuring 
the  intima  of  the  artery  by  stretching  it  too  much. 
Usually  there  will  be  no  difficulty  in  obtaining  a  large 
vein,  but  the  artery  may  be  very  small.  If  too  small 
a  cannula  is  used  the  volume  of  the  flow  will  be  di- 
minished. iMoreover,  too  large  a  vein  will  take  up  too 
much  room  in  the  cannula  and  the  amount  of  the  flow 
will  be  diminished. 

"  The  exposed  vessels  should  be  kept  moist  and 
warm  with  normal  salt  solution.  Not  only  is  drjdng 
harmful,  but  the  flow  is  increased  through  gradual 
relaxation  of  the  arterial  wall. 


94  BLOOD  TRANSFUSION 

"  Experience  has  shown  that  if  anything  goes 
wrong  in  carrying  out  this  technic,  it  is  best  to  start 
again  from  the  beginning,  and  not  to  try  to  get  around 
any  of  the  details  by  substitution." 

Elsberg's  Method 
The  second  cannula  is  an  ingenious  device  of  Els- 
berg.  It  is  built  on  the  principle  of  a  monkey-wrench 
(Fig.  6)  which  can  be  enlarged  or  narrowed  to  any 
size  desired  by  means  of  a  screw  at  its  end.  The 
smallest  lumen  obtainable  is  about  equal  to  that  of  the 


Fig.  6. — Elsberg's  monkey-wrench  cannula. 

smallest  Crile  cannula,  and  the  largest  greater  than 
the  lumen  of  any  radial  artery.  The  instrmnent  is 
cone-shaped  at  its  tip,  a  short  distance  from  which  is  a 
ridge  with  four  small  pin  points  which  are  directed 
backward.  The  lumen  of  the  cannula  at  its  base  is 
larger  than  at  the  tip.  The  construction  of  the  can- 
nula can  be  easily  understood  from  the  following 
description  of  the  method  of  using  it: 

"  The  radial  artery  of  the  donor  is  exposed  and 
isolated  in  the  usual  manner.     The  cannula,  screwed 


METHODS  OF  TRANSFUSION 


95 


wide  open,  is  then  slipped  under  and  around  the 
vessel.  It  is  then  screwed  shut  until  the  two  halves 
of  the  instrument  slightly  compress  the  vessel  (Fig. 
7).  The  artery  is  then  tied  off  about  one  centimetre 
from  the  tip  of  the  cannula.  Before  the  vessel  is, 
divided,  the  three  small-eye  tenacula  are  passed 
through  the  wall  of  the  artery,  at  three  points  of  its 
circumference,  a  few  millimetres  from  the  ligature. 
Small  mosquito  forceps  may  also  be  used.      These 


Fig.  7. 


Fig.  8. 


Fig.  9. 


Fig.  7. — Arterj-  "set"  in  Elsberg's  cannula;  tenacula  in  position  for  cuffing. 

Fig.  8. — Artery  everted  and  impaled  on  the  hooks.     Vein  grasped  by  mosquito  clamps. 

Fig.  9. — Cannula  slipped  into  side  of  vein  and  tied  in  position.    Anastomosis  complete. 

are  given  to  an  assistant,  who  makes  traction  on  them 
while  the  operator  cuts  the  vessel  near  the  ligature. 
The  moment  the  artery  is  cut,  the  stump  is  pulled 
back  over  the  cannula  by  means  of  the  tenacula  or 
forceps,  and  is  held  in  place  without  ligation  by 
the  small  pin-points  (Fig.  8).  There  is  no  bleeding 
from  the  artery,  even  though  no  haemostatic  clamp  has 
been  applied,  because  the  cannula  itself  acts  as  a 
haemostatic  clamp.     The  vein  of  the  recipient  is  then 


96  BLOOD  TRANSFUSION 

exposed  (but  not  freed),  two  ligatures  are  passed 
around  it,  one  is  tied  peripherally  in  the  usual  manner. 
A  small  transverse  slit  is  made  in  the  vein,  the  can- 
nula with  the  cuffed  artery  inserted  into  the  vein,  a 
ligature  tied  around  the  vein  and  cannula  screwed 
open  (Fig.  9)  and  the  blood  allowed  to  flow.  The 
rapidity  of  the  flow  can  be  varied  as  desired  by  the 
size  to  which  the  instrument  is  screwed  or  unscrewed, 
and  the  lumen  of  the  arteiy  is  never  diminished. 

"  It  >yill  be  noticed  that  the  arteiy  is  cufl'ed  instead 
of  the  vein ;  this  method  I  believe  to  be  more  correct. 
The  vein  is  the  larger  vessel  and  can  therefore  be  more 
easily  telescoped  over  the  artery.  The  vein  is  only 
exposed,  not  freed,  and  the  artery  is  intubated  into  it. 

"  With  this  cannula  I  have  been  able  to  make  the 
anastomosis  in  less  than  four  minutes  after  the  artery 
had  been  isolated,  and  have  found  the  entire  procedure 
a  simple  one.  The  advantages  of  the  instrument  are 
the  following: 

"  ( 1 )    One  cannula  will  fit  any  vessel. 

"  (2)  The  cannula  is  applied  around  the  vessel  in- 
stead of  the  vessel  being  drawn  through  the  cannula. 

"(3)   No  ligature  of  the  cufl'ed  vessel  is  required. 

"(4)  The  cannula  itself  acts  as  a  haemostatic 
clamp. 

"(5)  The  cufling  of  the  artery  is  easily  accom- 
plished without  stripping  back  the  adventitia,  and. 


METHODS  OF  TRANSFUSION  97 

tlieref  ore,  the  traumatism  to  the  artery  wall  is  reduced 
to  a  minimum. 

"  ( 6 )  The  vein  need  only  be  exposed,  not  dissected 
out  and  cut. 

"(7)  As  the  cannula  is  unscrewed  the  blood  will 
flow,  the  flow  can  be  regulated  at  will,  and  the  lumen 
of  the  artery  is  not  diminished." 

Beenheim's  Method 

The  third  instrument  which  I  shall  present  is  one 
of  my  own  design.  Simple  in  construction,  large 
enough  to  work  with  comfortably,  it  requires  a  mini- 


FiG.   10. — Author's  two-pieced  transfusion  tube. 

mum  of  dissection  and  can  be  rapidly  put  into  action. 
It  is  a  two-pieced  afl*air  (Fig.  10)  consisting  of  two 
hollow  tubes,  each  4  cm.  long,  and  each  bulbous  at  one 
end  in  order  to  form  a  neck  for  a  retaining  tie  or 
specially  devised  clamp,  and  bevelled  to  facilitate 
entrance  into  the  vessel;  the  other  ends  are  tubular 
and  fitted  for  invagination.  The  instrument  was  orig- 
inally constructed  in  two  sizes  as  regards  the  bore  of 
the  smaller  ends,  but  experience  has  shown  that  either 


W  BLOOD  TRANSFUSION 

size  will  fit  the  vessels  of  any  individual — from  an 
infant  up  to  an  adult. 

My  reason  for  having  an  instrument  thus  con- 
structed in  two  separate  parts  was  twofold.  First, 
in  transfusing  an  infant,  it  is  usually  difficult  to  make 
the  actual  union  of  vessels  with  a  small  instrument  like 
that  of  Crile  or  Elsberg  because  of  the  smallness  of 
the  parts  and  the  delicacy  of  the  infant's  vessels. 
Paraffined  glass  tubes  answer  the  pm*pose  fairly  well, 
but  paraffin  is  not  always  at  hand,  nor  is  a  suitable 
glass  tube,  and,  if  it  is,  the  probabilities  are  that  it  will 
be  chipped  or  broken.  Second,  for  emergency  work, 
I  believe  that  a  cannula  constructed  in  two  pieces,  one 
of  which  can  be  rapidly  inserted  into  the  artery  of  the 
donor,  and  the  other  into  the  vein  of  the  recipient,  by 
separate  screws  of  operators,  is  best.  Even  in  cases 
where  haste  has  not  been  so  urgent,  the  ordeal  for  the 
recipient,  who  is  usually  anxious  and  in  a  precarious 
state,  can  be  materially  relieved  by  preparing  the 
donor  completely  before  bringing  the  recipient  into 
the  operating  room,  or  even  by  preparing  the  two 
entirely  in  separate  rooms,  simply  wheeling  the 
stretcher  of  the  donor  into  the  recipient's  room,  placing 
them  in  apposition,  and  invaginating  the  two  halves 
of  the  cannula — ^a  matter  of  only  a  few  seconds. 

The  technic,  then,  of  a  transfusion  by  means  of 
this  two-pieced  cannula,  as  well  as  the  management 


METHODS  OF  TRANSFUSION  99 

of  direct  transfusion  in  general,  is*ias  follows:  The 
radial  artery  of  the  donor  is  usually  united  to  one  of  the 
superficial  veins  at  the  elbow  of  the  recipient;  occa- 
sionally because  of  infection  at  the  elbow,  it  becomes 
necessary  to  employ  a  vein  of  the  leg,  generally  the 
internal  saphenous,  although  any  available  vein  may 
be  used.  But  no  matter  whether  it  be  arm  to  arai, 
or  arm  to  leg,  in  preparing  the  patient  the  watchword 
should  be  "  left  to  left,  right  to  right " — in  other 
words,  the  left  radial  should  always  be  united  to  a 
vein  of  the  left  arm  or  leg  and  vice  versa;  a  few 
moments'  thought  will  show  the  anatomical  reasons 
for  this.  Other  things  being  equal,  it  is  always  wise 
to  leave  the  choice  of  radials  to  the  donor,  but  where 
he  (or  she)  has  no  choice,  it  is  my  rule  to  utilize  the 
left  radial,  if  the  patient  be  right-handed  and  both 
radials  are  of  the  same  size  ( which,  by  the  way,  is  not 
always  the  case) ,  his  right  if  he  be  left-handed.  Thus 
the  donor  will  be  incapacitated  as  little  as  possible 
during  the  healing  of  his  wound — a  detail,  perhaps, 
but  one  that  ought  to  be  considered. 

Time  will  be  saved  if  the  radial  is  dissected  out  as 
follows,  novocaine  (0.5  per  cent.)  being  the  anaes- 
thetic of  choice:  (1)  Expose  the  artery  with  its 
accompanying  veins  for  a  distance  of  about  two  inches ; 
(2)  free  the  artery  from  the  veins  and  tie  off  all 
branches  doubly  with  very  fine  silk,  cutting  between 


100  BLOOD  TRANSFUSION 

the  ties;  (8)  tie  off  the  artery  doubly  at  the  distal 
end  of  the  wound  and  cut  between  the  ties,  thus  allow- 
ing about  one  and  one-half  inches  of  the  vessel  to  lie 
free  in  the  wound;  (4)  tie  off  all  bleeding  points  in 
the  wound,  and  keep  a  constant  stream  of  warm  salt 
solution  flowing  over  the  artery,  all  sponging  being 
done  with  gauze  moistened  in  the  same  solution ;  ( 5 ) 
place  a  bull-dog  clamp  on  the  vessel  at  the  proximal 
end  of  the  wound. 

Up  to  this  point  the  technic  is  the  same  no  matter 
which  method  of  anastomosis  is  to  be  used.  If  my 
two-pieced  cannula  is  to  be  employed,  a  small  cut  is 
now  made  in  the  upper  side  of  the  artery  with  a  fine 
pair  of  scissors  or  a  knife,  the  opening  being  made  at 
right  angles  to  the  course  of  the  vessel  and  about 
half  its  width.  Next,  every  visible  trace  of  blood 
is  immediately  washed  out  with  warm  salt  solution 
and  liquid  vaseline,  the  latter  being  injected  into  the 
lumen  of  the  vessel  with  a  medicine  dropper  at  fre- 
quent intervals  during  the  washing  process.  It  keeps 
the  vessel  soft  and  pliable,  and  prevents  too  rapid 
evaporation  and  consequent  drying.  Any  little  bit 
of  adventitia  that  may  get  into  the  opening  should 
be  carefully  pushed  away  or  cut  off. 

The  vessel  having  been  carefully  prepared,  the 
bevelled  end  of  the  male  half  of  the  tube  is  inserted 
in  the  artery  and  held  there  by  a  tie  thrown  around  its 


■  \ 

METHODS  OF  TRANSFUSION  101 

neck  ( Fig.  11 ) ."  Liquid  vaseline  is  now  again  injected 
into  the  vessel  through  the  tube,  and  the  whole  thing 
wrapped  in  salt  solution  gauze  to  await  the  completion 
of  a  similar  preparation  of  the  vein  of  the  recipient. 
It  is  hardly  necessary  to  dissect  out  more  than  one 
inch  of  the  vein,  and,  as  this  is  always  quite  super- 
ficial, the  time  required  for  the  whole  procedure  of 
dissection,  cleansing,  and  insertion  of  the  female  half 
of  the  tube  amounts  to  hardly  more  than  five  minutes. 
When  both  patients  have  been  prepared,  their 
stretchers  are  brought  into  apposition  and  the  two 
arms  are  placed  on  a  table  about  one  foot  broad.  With 
a  little  manipulation  the  wrist  of  the  donor  is  brought 
into  such  proximity  to  the  elbow  of  the  recipient  that 
the  tubes  can  be  invaginated  to  the  proper  degree 
(Fig.  12).  When  this  is  accomplished,  a  steady 
stream  of  warm  salt  solution  is  started  flowing  over 
the  artery,  tubes,  vein,  and  the  bull-dog  clamp  is 
removed  from  the  vein,  its  place  being  taken  by  the 
thumb  and  the  first  finger  of  the  right  hand  of  the 
operator.  With  great  care  the  clamp  controlling  the 
arterial  flow  is  now  gradually  released,  coincidently 
with  which  the  thumb  and  finger  controlling  the  vein 
gradually  ease  up,  thus  permitting  the  blood  to  go 

-  A  special  clamp  has  been  devised  for  this  purpose,  thus 
obviating  the  necessity  of  using  a  single  tie  during  the  course 
of  the  transfusion — except  for  closing  purposes. 


102 


BLOOD  TRANSFUSION 


Fig.  11. — Bernbeim's  Trau-sfusiwn  of  lilood. 


Fig.   12. — Tubes  invaginated  and  anastomosis  complete. 


104  BLOOD  TRANSFUSION 

over  gradually,  so  as  to  prevent  any  possibility  of 
swamping,  or  embarrassing  the  circulation  of  the  re- 
cipient by  a  sudden  gush  of  blood  under  great  pres- 
sure. Let  it  be  strongly  emphasized  here  that,  with 
few  exceptions,  the  margin  of  safety  is  none  too  great 
in  any  transfusion  at  any  stage.  It  is  wise,  therefore, 
to  control  the  inflow  in  the  manner  above  described 
during  the  entire  course  of  the  transfusion. 

If  assistants  are  at  hand,  the  blood-pressure  and 
pulse  of  the  recipient  should  be  taken  at  inten^als  of 
every  three  minutes,  that  of  the  donor  eveiy  five  min- 
utes. These  measures  cause  but  slight  annoyance  to 
the  patients  and  are  of  the  utmost  importance  to  the 
surgeon  in  judging  the  condition  of  both  individuals. 
Ha?moglobin  and  red  counts,  made  during  the  course 
of  the  operation,  although  they  are  interesting  and  val- 
uable, do  not  give  nearly  so  helpful  immediate  infor- 
mation as  do  blood-pressure  and  pulse,  and,  since  they 
cause  more  or  less  discomfort  to  the  patients,  we  do 
not  make  these  readings  unless  there  is  some  special 
reason  for  them.  It  is  unnecessary  to  say,  of  course, 
that  the  blood-pressure  and  pulse  of  both  donor  and 
recipient  have  been  taken  before  starting  the  trans- 
fusion, as  a  control,  and  that  if  the  facilities  are  at 
hand,  a  complete  blood  examination — reds,  white,  and 
lijemoglobin — has  been  made  of  both  patients,  also  as 
a  control,  for  after  completion  of  the  transfusion  these 


METHODS  OF  TRANSFUSION  105 

data  are  most  valuable  in  interpreting  both  the  imme- 
diate and  future  results  of  the  operation. 

Where  the  recipient  is  practically  exsanguinated, 
and  there  is  no  contra-indication,  it  is  wise  to  give  him 
all  the  blood  he  can  conveniently  hold,  even  occasion- 
ally (Crile)  going  to  the  extent  of  using  two  donors 
in  case  one  cannot  stand  any  great  loss  of  blood.  ]My 
routine  is  to  attempt  to  bring  a  pulse  of  say  150  or 
160  down  to  about  100  and  to  raise  a  blood-pressure 
of  50  to  70  up  to  110  or  120,  figures  well  within  the 
zone  of  safety. 

It  sometimes  happens  that  it  is  decidedly  unwise, 
even  hazardous,  to  overload  the  circulation,  an  ex- 
ample of  such  a  case  being  a  patient  exsanguinated  as 
a  result  of  hemorrhage  from  typhoid  (or  other)  ulcers 
of  the  bowel.  To  give  such  an  individual  much  blood 
would  be  tempting  fate,  whereas  a  small  amount,  sent 
in  slowly,  will  decrease  the  coagulation  time,  and  seal 
up  the  mouths  of  open  vessels  with  life-saving  thrombi. 
In  other  words,  a  great  amount  of  blood  will  simply 
raise  the  blood-pressure  to  such  an  extent  that  it  will 
literally  blow  out  any  soft  young  plugs  that  might  be 
all  that  is  holding  body  and  soul  together. 

It  is  a  most  difficult  matter  to  judge  as  to  the  exact 
amount  of  blood  that  has  gone,  or  is  going  over.  No 
practical  method  of  measuring  the  amount  of  blood 
flow  in  a  direct    transfusion    has  been  devised,  and 


106  BLOOD  TRANSFUSION 

until  this  much-desired  instrument  is  placed  at  our 
disposal  we  shall  be  compelled  to  depend  upon  clinical 
signs  for  an  index  of  the  amount  of  blood  transfused. 
It  must  be  recognized  that  a  number  of  factors  must 
of  necessity  enter  into  any  calculation  of  bulk.  The 
blood-pressure,  because  of  the  psychic  disturbance  in 
every  operation  of  this  sort,  is  by  no  means  constant. 
The  loss  of  blood  is  another,  perhaps  the  chief,  factor 
in  determining  the  instability  of  the  blood-pressure 
and  therefore  the  amount  that  goes  over  in  bulk.  The 
pulse-rate  varies,  too,  from  time  to  time  and  this  must 
be  considered  in  any  determination  of  amount.  There 
are  still  other  factors,  such  as  the  viscosity  of  blood, 
etc.,  which  need  not  be  considered  in  a  work  of  this 
character.  It  is  sufficient  to  say  that  to  the  careful, 
experienced  surgeon  all  the  factors  above  mentioned 
can  be  determined  with  a  surprising  degree  of 
accuracy  by  the  thumb  and  forefinger  guarding  the 
entrance  to  the  vein.  This  knowledge  and  constant 
obsei'\'ation  of  the  actual  blood-pressure  reported  by 
the  assistants,  the  general  appearance  of  the  patients, 
and  the  actual  time  that  the  blood  has  been  flowing — 
all  these  serve  as  a  guide  to  the  amount  of  blood  going 
over,  and  the  proper  time  to  cease  transfusing. 

In  regard  to  the  duration  of  actual  flow  in  trans- 
fusion in  general,  there  are  various  questions  to  be 
considered.    An  infant  will  require  but  a  small  amount 


METHODS  OF  TRANSFUSION  107 

of  blood  (children  need  far  less  than  adults),  and,  as 
a  rule,  women  less  than  men,  always  considering  that 
the  patient  is  exsanguinated.  A  big  strong  man  will 
generally  have  a  larger  radial  than  a  small  man,  and 
his  pressure  will  enable  a  much  larger  and  more  power- 
ful stream  to  be  thrown  by  his  vessel.  Likewise,  a 
female  donor  may  give  less  blood  in  a  given  time  than 
a  man — provided  the  man  is  not  too  badly  frightened. 
Thus,  the  actual  time  of  transfusion  varies  from  three 
to  five  minutes  to  one  hour  or  even  an  hour  and  a 
quarter  if  a  very  small  cannula  is  used  or  if  the  blood 
has  been  permitted  to  go  over  very  slowly.  For 
most  transfusions  the  average  duration  of  the  flow  is 
from  twenty  to  forty  minutes. 

The  welfare  of  the  donor  in  transfusion  must  be 
carefully  watched.  I  have  transfused  from  one  donor 
for  over  an  hour  without  any  signs  of  distress,  while 
in  another  case  fifteen  minutes  were  sufficient  to  pro- 
duce great  anxiety.  In  general  a  sudden  fall  of 
twenty  to  thirty  points  in  blood-pressure  should  warn 
the  operator  that  the  limit  has  about  been  reached. 
Unfortunately,  however,  a  blood-pressure  apparatus 
is  not  always  at  hand  and  even  when  it  is,  the  fall  in 
pressure,  sudden  or  gradual,  does  not  always  occur. 
In  such  instances  any  sudden  pallor,  accompanied  by 
nausea  and  vomiting,  continued  and  increasing  thirst, 
great  restlessness,  together  with  a  decrease  in  blood- 


108  BLOOD  TRANSFUSION 

pressure  as  shown  by  the  finger  of  the  operator  on 
the  donor's  radfal,  may  sei-ve  as  the  needed  danger 
signal.  The  bleeding  should  never  be  permitted  to 
exceed  the  limit  of  safety;  the  donor  ought  never  be 
allowed  to  collapse  utterly.  A  proper  appreciation 
of  his  own  responsibility  as  well  as  the  moral  i-ights 
of  those  courageous  individuals,  generous  enough  to 
give  of  their  own  blood  that  another  might  live,  should 
always  be  pre-eminent  in  the  mind  of  the  surgeon  who 
undertakes  work  of  this  nature. 

INDIRECT    TRANSFUSION 

Coming  to  the  indirect  methods,  one  has  again  the 
opportunity  of  choice,  and  various  factors  influence 
one  in  a  determination  of  method,  such,  for  instance, 
as  the  number  of  assistants  at  hand,  the  ability  to 
move  the  patient  or  the  desirability  of  doing  so,  et 
cetera.  It  may  be  said  in  general  that  intimate  famil- 
iarity with  one  single  method  is  greatly  to  be  desired, 
although  a  working  knowledge  of  several  is  conducive 
to  the  best  results,  flexibility  in  matters  of  this  sort 
being  always  of  advantage. 

The  first  indirect  method  of  transfusing  blood  that 
was  of  any  real  practical  worth  was  devised  and  per- 
fected by  Dr.  Edward  Lindeman  of  New  York  and 
for  a  time  it  was  the  only  indirect  method  in  use. 
But  it  has  serious  drawbacks  in  that  three  assistants 


METHODS  OF  TRANSFUSION  109 

are  essential  to  its  proper  use  and  unless  the  "  team  " 
works  together  with  rapidity  and  precision,  certain 
accidents  may  take  place  of  such  character  that  the 
blood  transfer  is  delayed,  or  interfered  with,  or  even 
prevented.  So  that  modifications  of  Lindeman's 
method  presently  appeared,  one  of  which  was  devised 
by  Unger,  also  of  Xew  York,  another  by  myself, 
and  still  others  by  a  number  of  different  men,  the 
cardinal  principle  of  all  being  about  the  same  though 
differing  somewhat  in  construction  and  execution. 

Proceeding  along  somewhat  different  lines,  Kimp- 
ton  and  Brown  of  Boston  devised  an  indirect  method 
of  collecting  blood  in  a  paraffined  glass  cylinder  and 
then  injecting  it,  while  a  somewhat  similar  apparatus 
was  devised  by  Satterlee  and  Hooker. 

The  latest  method — and  the  one  that  really  holds 
out  more  promise  of  permanent  usefulness  than  any 
other — is  that  known  as  the  citrate  method  as  con- 
ceived and  perfected  by  Lewisohn  of  New  York  and 
almost  coincidentally  by  Agote  of  Argentina. 

Sodium  citrate  is  an  anticoagulant  long  known  to 
laboratory  workers,  and  used  by  them  experimentally, 
but  always  considered  too  toxic  for  human  use,  so  that 
when  Lewisohn  suggested  that  it  could  be  used  with 
perfect  safety  in  0.2  per  cent,  strength  solution,  a 
great  deal  of  skepticism  was  expressed  even  in  the  face 
of  his  carefully  planned  animal  experiments  and  his 


no  BLOOD  TRANSFUSION 

successful  clinical  demonstrations.  This  lack  of  en- 
thusiasm was  unfortunately  strengthened  by  a  few 
early  unsatisfactory'  reports  by  scattered  clinicians 
whose  work  did  not  bear  close  inspection.  Several 
deaths  were  chronicled  and  numerous  sequelae  were 
attributed  to  the  use  of  citrated  blood  that  have  been 
found  by  more  competent  observers  to  have  been  the 
result  of  errors  in  hemolytic  tests,  and  in  the  carrying 
out  of  the  actual  transfusion  technic,  rather  than  to 
the  use  of  citrate.  This  unsettled  state  of  affairs, 
though,  has  resulted  in  delaying  the  widespread  use 
of  the  method  and  has  to  a  certain  extent  cast  a  shadow 
over  its  many  merits.  For  there  can  be  no  question 
but  that  a  great  step  forward  was  taken  when  it  be- 
came possible  to  take  uncoagulable  blood  to  a  patient's 
room  and  in  a  leisurely  manner  have  it  pass  into  his 
veins  without  in  the  least  disturbing  him  other  than 
by  possibly  dissecting  out  a  small  segment  of  his  ves- 
sel— though  even  this  is  unnecessary  in  those  cases 
where  a  vein  of  sufficient  calibre  to  accommodate  a 
needle  can  be  seen  or  felt.  By  some  this  is  felt  to  be 
a  matter  of  small  importance,  but  such  a  view  can 
only  be  held  by  the  inexperienced.  Those  who  have 
actually  witnessed  exitus  of  the  desperately  ill  as  a 
result  of  or  during  the  comparative  slight  manipu- 
lations necessary  to  a  transfer  from  bed  to  stretcher 
or  even  from  moving  the  bed  on  to  or  off  of  an  elevator 


METHODS  OF  TRANSFUSION  111 

know  better.  Even  where  actual  demise  does  not  fol- 
low, it  is  a  well  known  fact  that  simple  transfer  of 
patients  from  the  ward  or  room  to  the  operating  room 
lowers  their  overtaxed  vitality.  I  cannot  lay  too  much 
stress  on  this  point. 

Xor  is  this  the  only  claim  for  recognition  of  the 
citrate  method,  since  by  this  method  transfusions  in 
the  home  will  be  greatly  facilitated  and  at  no  time 
will  it  be  necessarj^  for  patient  to  see  donor  or  vice 
versa,  I  do  not  mean  to  advocate  transfusion  in  the 
home — on  the  contrary,  it  is  to  be  avoided — but  every 
once  in  a  while  cases  of  the  utmost  urgency  arise  where 
it  becomes  necessary  to  cany  out  a  transfusion  in  the 
home,  a  rather  difficult  and  tiresome  procedure,  until 
now.  The  separation  of  donor  from  recipient  elimi- 
nates at  one  fell  blow  the  depressing  psychical  element 
from  blood  transfusion,  a  most  fortunate  event,  espe- 
cially in  cases  where  near  and  dear  relatives  act  in 
these  capacities.  The  Kimpton-BrowYi  method  of 
transfusion  some  time  ago  eliminated  this  feature  to 
a  degree  but  it  has  certain  drawbacks  common  to  all 
methods  where  whole  untreated  blood  is  used  that 
are  not  to  be  found  in  the  citrate  method. 

I  have  used  many  different  insti-uments  for  trans- 
fusion, several  of  which  I  devised,  and  I  have  passed 
through  the  successive  stages  of  fearfully  difficult  and 
trj^ing  direct  transfusion  with  Crile's  tube  and  my 


112  BLOOD  TRANSFUSION 

little  three-pronged  modification,  to  the  direct  trans- 
fusion with  longer  glass  and  metal  tubes.  And  from 
that  stage,  along  with  the  other  workers,  I  passed  to 
the  period  of  indirect  transfusion  by  Lindeman's 
needle  and  syringe,  which  for  a  time  seemed  to  satisfy 
— but  only  for  a  time,  because  of  its  clumsiness.  ^Nlodi- 
fications  of  this  method  then  made  their  appearance  in 
the  form  of  tubes  containing  a  central  revolving  plug, 
one  of  which  I  devised  and  used  many,  many  times 
with  the  utmost  success  and  satisfaction — as  did  many 
others.  But  I  am  frank  to  admit  that  no  method  and 
no  instrument  is  comparable  in  facility  and  elas- 
ticity to  the  citrate  method  of  transfusion  and  I  feel 
that  a  debt  of  gratitude  is  owing  to  Drs.  Lewisohn, 
Weil,  and  Agote  for  working  out  its  details  so  care- 
fully. Of  late  I  have  used  this  method  in  preference 
to  all  others  and  venture  to  predict  that  within  a  few 
years  all  our  cunningly  devised  instruments  for  trans- 
fusion will  be  of  interest  merely  as  curiosities.  They 
have  served  their  purpose  admirably  but  their  day  is 
waning. 

My  reason  for  giving  a  few  of  the  indirect  methods 
of  transfusion  is  that  they  are  still  in  use  to  a  great 
extent  and  will  probably  continue  to  be  employed, 
although  in  decreasing  proportion  as  the  citrate 
method  becomes  more  familiar. 


METHODS  OF  TRANSFUSION  113 

LiNDEMAX's   MeTHOB 

"  The  entire  apparatus  for  simple  syringe  transfu- 
sion consists  of  two  sets  of  cannulas,  two  tourniquets 
and  twelve  syringes. 

CANNULAS 

"  Two  sets  of  cannulas  are  employed,  one  for  the 
donor,  the  other  for  the  recipient. 

There  are  three  cannulas  to  each  set  (Fig.  13, 
1,  2,  3).  Each  cannula  telescopes  within  the  other 
as  shown  in  Fig.  14. 

The   innermost   cannula   is   practically   a   hollow 


1 
z 


riENANN. 

Fig.  13. 


needle,  2  6/16  inches  long,  20-gauge,  with  one  end 
ground  to  a  fine  point  and  short  bevel.  The  hollow 
needle  (1,  Fig.  14)  is  fitted  snugly  into  cannula  2. 
Cannula  2  is  5  mm.  shorter  than  the  needle  and  is 


fitted  snugly  into  cannula  3.     Cannula  3  is  5  mm. 


8 


114  BLOOD  TRANSFUSION 

shorter  than  cannula  2.  The  proximal  ends  of  1  and 
2  are  capped  with  stationary  thumb-screw  caps. 

The  proximal  end  of  3  is  capped  with  a  receiver  to 
fit  any  Record  syringe. 

Cannula  3  is  2  inches  long,  14-gauge,  .064  diame- 
ter. The  calibre  of  this  cannula  is  the  same  as  the 
tip  of  a  Record  syringe. 

In  very  small  infants  with  very  small  veins  only 
cannulas  1  and  2  are  employed,  2  being  capped  with 
the  receiver  to  fit  tip  of  syringe. 

The  syringes  used  are  Record  syringes  of  new 
improved  type  with  a  capacity  of  20  c.c.  and  can  be 
sterilized  by  boiling. 

OPERATION 

*'  One  operator  manages  syringe  of  recipient.  An- 
other operator  manages  syringe  of  donor.  An  assist- 
ant stands  between  operators,  who  are  in  a  position 
close  to  the  assistant.  Donor  and  recipient  are  placed 
in  the  recumbent  posture.    Suitable  veins  are  selected. 

In  adults  and  most  childi'en  over  two  years  of  age 
the  median  basilic  is  easily  accessible.  In  infants  the 
external  jugular  or  one  of  its  tributaries  is  entered 
more  advantageously.  In  some  cases  the  internal 
saphenous  may  prove  the  vein  of  preference. 

A  tourniquet  is  placed  in  position,  and  the  skin 
is  sterilized  with  iodine.  The  cannula  is  then  held 
in  a  position  almost  parallel  to  the  vein  with  the  thumb 


METHODS  OF  TRANSFUSION  115 

on  the  thumb-screw  cap  of  the  innermost  cannula 
(1,  Fig.  1J<).  The  skin  is  then  punctured  and  the 
cannula  is  forced  into  the  vein.  After  the  first  joint 
A  has  entered  vein,  Cannula  I  is  withdrawn  a  dis- 
tance of  about  one-half  inch.  ( This  prevents  the  ves- 
sel wall  from  being-  injured  or  punctured  by  the 
needle  after  the  vein  is  entered.) 

With  the  thumb  now  on  the  thumb-screw  cap  of  2 
the  cannula  is  forced  in  until  the  second  joint  B  (Fig. 
14)  has  entered  the  vein.  Cannula  2  is  then  with- 
drawn a  distance  of  about  one-half  inch  (cannula  3 
alone  can  come  into  contact  with  the  vessel  wall). 
Cannula  3  is  then  gently  pushed  into  the  vein  to  a 
desirable  length;  usually  three-quarters  to  one  inch 
will  suffice. 

Cannulas  1  and  2  are  now  withdrawn  entirely.  If 
the  vein  has  been  successfully  entered,  blood  will  flow 
through  the  cannula.  When  the  first  drop  appears  a 
syringe  containing  warm  saline  solution  is  imme- 
diately attached  and  a  very  slow  flow  of  saline  is  main- 
tained through  cannula.  Escape  of  blood  is  thus 
prevented. 

There  is  no  need  of  haste  at  this  stage. 

A  cannula  is  next  inserted  in  vein  of  donor  in  a 
like  manner;  again  a  syringe  containing  warm  saline 
is  attached  and  loss  of  blood  thus  prevented.  Every- 
thing is  now  in  readiness  for  the  transfusion.     An 


116  BLOOD  TRANSFUSION 

empty  syringe  is  substituted  for  the  one  containing 
saline  solution,  and  blood  is  withdrawn  from  donor 
as  rapidly  as  possible.  When  the  syringe  is  full  the 
assistant  passes  it  to  the  operator  on  the  recipient, 
who  removes  its  saline  syringe,  attaches  the  syringe 
containing  blood  and  evacuates  the  contents  gently 
but  speedily  into  the  vein. 

One  syringeful  of  blood  is  followed  by  another 
in  rapid  succession  until  the  desired  quantity  of  blood 
has  been  transfused. 

A  little  normal  saline  is  injected  through  cannula 
of  recipient  after  each  syringeful  of  blood.  This  keeps 
cannula  free  of  blood  and  precludes  the  possibility 
of  clotting. 

It  has  been  found  advisable  for  the  assistant  (or 
third  man)  to  remove  the  syringe  from  the  cannula  of 
the  donor  as  soon  as  filled.  The  operator  can  thus 
hold  the  cannula  in  place  with  one  hand  while  with  the 
other  hand  he  may  at  once  adjust  an  empty  syringe 
into  the  cannula.  Loss  of  blood  is  thus  reduced  to  a 
minimum. 

RULES 

"  1.  Bright  polished  surfaces  of  syringe  and  can- 
nulas are  requisite. 

2.  A  syringe  used  once  should  not  again  be  em- 
ployed until  thoroughly  cleansed  with  sterile  water. 


METHODS  OF  TRANSFUSION  117 

3.  Air  must  be  avoided.  This,  however,  offers  no 
difficulty. 

4.  Tourniquet  of  patient  must  be  removed  after 
vein  is  entered  with  cannula. 

5.  Tourniquet  remains  on  donor  throughout  oper- 
ation; momentary  release  of  tourniquet  may  be  advis- 
able once  or  twice  during  course. 

6.  Dexterity  and  speed  are  requisite  for  success. 

7.  Syringes  can  be  evacuated  more  rapidly  than 
they  can  be  filled  without  any  harmful  effects.  This 
difference  in  time  allows  for  attachment  of  syringe 
with  warm  saline  following  each  syringeful  of  blood. 

COMMENTS 

"  The  time  elapsing  in  filling  and  evacuating  the 
syringe  is  so  brief  that  blood  does  not  undergo  any 
alteration  from  donor  to  recipient. 

Xo  lubricant  has  been  employed  except  in  one 
case.  Cannulas  are  lined  with  a  film  coating  of 
albolene. 

Both  arms  of  the  donor  may  be  used  simul- 
taneously. 

Larger  syringes  with  larger  calibred  cannulas  may 
be  used,  but  the  present  sizes  have  worked  satisfac- 
torily and  fittings  of  syringe  and  cannulas  are  of  uni- 
versal gauge. 

Syringes  and  cannulas  may  be  kept  sterile  in  indi- 
vidual metal  containers.     They  are  thus  in  readiness 


118  BLOOD  TRANSFUSION 

for  immediate  use  and  no  preparation  for  operation  is 
required. 

The  same  vein  can  be  used  repeatedly  for  subse- 
quent transfusions,  since  no  thrombosis  nor  permanent 
injuiy  to  vessel  occurs. 

Any  quantity  of  blood  can  be  transfused  and 
the  quantity  is  definitely  measured  at  the  time  of 
transfusion." 

Unger's  Method, 
"  The  instrument  (Fig.  15)  I  have  devised  elimi- 


Fio.  15. — Unger's  instrument  for  indirect  transfusion.    {J.  A.  M.  A.,  February  13,  1915, 

vol.  Ixiv,  No.  7.) 

nates  the  causes  of  the  difficulties  experienced  in  the 
syringe-cannula  method.  Fundamentally,  it  is  a  stop- 
cock, which  alternately  connects  a  syringe  for  blood 
to  the  donor  and  at  the  same  time  a  syringe  with 
saline  to  the  recipient;  then  by  turning  the  cock  the 
syringe  with  blood  is  immediately  connected  to  the 
recipient  and  the  syringe  with  saline  to  the  donor. 


METHODS  OF  TRANSFUSION  119 

THE  INSTRUMENT 

"  A  cock  which  has  four  outlets  constitutes  the  cen- 
tral part  of  the  instrument.  The  outlets  are  desig- 
nated as  follows:  (1)  Blood  outlet  (B) ;  (2)  saline 
outlet  (S)  ;  (3)  recipient's  outlet  (R)  ;  (4)  donor's 
outlet  (D). 

(1)  Blood  outlet  (B)  :  To  this  is  directly  attached 
a  20  c.c.  "Reformed  Record"  syringe  (Syr.). 
Through  this  outlet,  by  means  of  the  syringe,  the 
blood  is  aspirated  or  injected. 

(2)  Saline  outlet  (S)  :  To  this  is  attached  a  long 
piece  of  rubber  tubing,  the  other  end  of  which  has 
connected  to  it  a  syringe  for  saline.  The  exact  length 
of  the  tube  is  immaterial.  It  should,  however,  be 
long  enough  to  get  the  assistant  who  is  attending  to 
the  injection  of  saline  out  of  the  way  of  the  operator. 
The  material  of  which  the  tube  is  made  is  likewise 
unimportant,  since  nothing  but  saline  passes  through 
it.  Instead  of  a, plain  syringe,  a  slightly  modified 
Wechselmann  salvarsan  apparatus  may  be  used.  The 
latter,  by  means  of  two  ball-valves,  allows  of  the  ready 
filling  and  emptying  of  the  syringe,  and  eliminates  the 
necessity  of  disconnecting  it. 

(3)  and  (4)  Recipient's  and  donor's  outlet  (R 
and  D)  :  To  each  of  these  is  connected  a  paraffined 
rubber  tube  1^  inches  long,  which  has  attached  to  its 
other  end  a  metal  connecting  piece.    This,  in  turn,  fits 


120  BLOOD  TRANSFUSION 

the  recipient's  and  donor's  cannula.  The  tubing  is  a 
piece  of  catheter  (No.  15  French)  which  is  paraffined 
according  to  the  method  described  by  Dr.  G.  E. 
Brewer.  They  are  sterihzed,  and  then  for  a  few  sec- 
onds immersed  in  boihng  paraffin.  The  tube  is  then 
shaken  in  the  air  in  order  to  distribute  the  par- 
affin equally,  to  get  rid  of  the  excess,  and  to  hasten 
hardening. 

The  cock  is  so  arranged  that  the  central  stopper 
(CS)  can  be  rotated  only  through  an  arc  of  45  de- 
grees. This  range  of  rotation  allows  of  three  possible 
positions,  in  two  of  which  two  sinmltaneous  circuits 
exist;  in  the  third  no  circuit  whatever  is  present. 
Naming  the  positions  according  to  the  flow  of  blood 
and  the  circuits  according  to  the  outlets  they  connect, 
we  have: 

1.  Donor's  position,  establishing  (a)  donor  blood 
circuit  and  (b)  recipient  saline  circuit. 

2.  Recipient's  position,  establishing  (a)  recipient 
blood  circuit  and  (6)  donor  saline  circuit. 

3.  Intermediate  position,  establishing  no  circuit — 
all  outlets  are  shut  off. 

1.  Donor's  position :  If  the  cock  be  turned  toward 
the  donor  as  far  as  it  will  go,  the  instrument  will  be 
in  the  donor's  position.  A  channel  (donor  blood  cir- 
cuit) between  the  donor's  vein  and  the  Record  syringe 
is  established  for  the  aspiration  of  blood.    At  the  same 


METHODS  OF  TRANSFUSION  121 

time,  another  channel  (recipient  saline  circuit)  exists, 
through  which  saline  is  injected  into  the  recipient's 
cannula  in  order  to  insure  its  patency. 

2.  Recipient's  position:  If  the  cock  be  turned  to- 
ward the  recipient  as  far  as  it  will  go,  the  instrument 
will  be  in  the  recipient's  position.  Here  again,  two 
channels  exist,  one  through  which  the  blood  is  injected 
into  the  recipient  (recipient  blood  circuit),  and  one 
(donor  saline  circuit)  which  connects  the  donor  with 
the  saline  syringe  so  that  this  circuit  can  be  kept 
patent.  It  is  this  immediate  and  continued  flushing 
with  saline  of  that  part  of  the  system  through  which 
blood  is  not  passing  that  insures  freedom  from  clotting. 

3.  Intermediate  position:  If  the  cock  be  turned 
midway  between  the  donor's  and  the  recipient's  posi- 
tions, the  instrument  is  in  the  intermediate  position, 
and  all  the  outlets  are  closed  off. 

The  instrument  is  supported  by  a  stand,  which 
is  merely  a  mechanical  device  to  hold  the  cock  station- 
ary and  to  permit  of  its  adjustment  to  various  heights 
in  conformity  with  the  levels  of  the  veins. 

TECHXIC 

"  After  having  firmly  fixed  the  stand  to  the  table 
the  cock,  with  the  tubing  attached  to  the  donor's  and 
recipient's  outlets,  is  fastened  to  the  stand.    The  saline 
apparatus,  from  which  all  air  has  been  forced  out,  is 


122  BLOOD  TRANSJ'USION 

connected  to  the  saline  outlet.  The  cock  is  put  in  the 
donor's  position  and  here  also  the  air  is  forced  out 
by  means  of  saline.  By  raising,  lowering,  or  rotating 
the  pedestal,  to  which  the  instrument  is  attached,  and 
by  proper  placing  of  the  arms,  connections  to  the  can- 
nulas can  be  made  without  difficulty. 

Into  the  recipient's  vein  is  inserted  a  large  qannula, 
which  is  then  connected  to  the  recipient's  outlet.  Since 
the  cock  is  in  the  donor's  position,  saline  can  be  slowly 
injected  into  the  recipient,  thereby  insuring  the  pa- 
tency of  this  cannula.  Into  the  donor's  vein  is  inserted 
a  cannula  which  is  now  attached  to  the  donor's  outlet. 
It  is  important  to  insert  the  cannula  so  that  it  points 
toward  the  donor's  hand  rather  than  the  tourniquet. 
Blood  immediately  runs  out  of  the  blood  outlet,  forc- 
ing the  air  ahead  of  it.  Into  this  outlet,  a  Record 
syringe  is  placed  and  blood  aspirated.  When  the 
syringe  is  filled,  the  cock  is  turned  into  the  recipient 
ppsition  and  the  blood  injected.  Since  the  assistant 
is  always  very  slowly  injecting  saline,  he  is  now  flush- 
ing the  circuit  which  was  used  in  getting  the  blood  into 
the  syringe.  As  soon  as  the  20  c.c.  of  blood  have  been 
injected,  the  cock  is  turned  back  to  the  donor's  posi- 
tion, and  the  syringe  refilled.  This  is  continued  until 
the  desired  amount  of  blood  has  been  transfused.  The 
syringe  need  not  be  changed  after  each  injection,  but 
may  be  refilled  until  it  begins  to  work  with  difficulty. 


METHODS  OF  TRANSFUSION  128 

Before  the  syringe  is  disconnected,  the  cock  should 
be  turned  to  the  intermediate  position  so  that  there  is 
no  loss  of  blood. 

After  connections  have  been  made  to  the  cannulas : 
(1)  The  operator  (a)  aspirates  and  injects  blood, 
(b)  changes  the  syringe  when  necessary  and  (c)  turns 
the  cock  back  and  forth.  (2)  The  assistant  merely 
slowly  forces  saline  out  of  his  syringe.  ( 3 )  The  nurse 
cleans  the  Record  syringes  as  fast  as  they  are  used  and 
places  a  clean  one  in  easy  reach  of  the  operator. 

ADVANTAGES   OF    THIS    METHOD 

"  The  instrument  I  have  described  overcomes  the 
difficulties  experienced  with  the  syringe-cannula 
method,  by  striking  at  their  causes. 

1.  The  frequent  handling  of  the  cannulas  is  elimi- 
nated because  the  connections  are  made  not  directly 
to  them  but  to  the  cock.  For  this  reason  the  cannulas 
ought  not  to  be  dislodged. 

2.  Clotting  is  avoided  because  the  entire  system  is 
regularly  and  instantly  flushed  with  saline,  and  the 
length  of  time  the  blood  is  outside  of  the  body  is 
reduced  to  a  minimum.  In  none  of  the  animal  experi- 
ments did  clotting  occur. 

3.  Only  the  operator  handles  the  blood  syringe. 
The  function  of  the  assistant  is  limited  to  the  injection 
of  saline. 


124  BLOOD  TRANSFUSION 

4.  Fewer  syringes  are  needed.  In  one  experi- 
ment, 800  c.c.  of  blood  were  transfused,  only  two 
syringes  being  used.  It  is  advisable,  however,  to  have 
about  four  to  meet  emergencies. 

5.  It  is  time-saving  because  it  reduces  the  manipu- 
lations; it  minimizes  the  time  the  blood  is  outside  of 
the  body,  and  it  allows  of  the  injection  of  saline  simul- 
taneously with  the  aspiration  or  injection  of  blood. 
When  indicated,  a  more  rapid  transfusion  can  be  done 
by  this  than  by  any  other  method.  The  rate  of  flow 
can,  however,  be  varied  at  will.  Blood  can  be  sent 
across  as  slowly  as  one  wishes,  because  the  patency  of 
the  circuits  can  be  relied  on." 

Bernheim's  Method 

"  Briefly,  the  apparatus  consists  of  two  needles,  one 
of  which  is  inserted  into  a  vein  of  the  donor,  the  other 
into  a  vein  of  the  recipient,  and  a  U-shaped  tube,  at 
the  midpoint  of  which  is  a  pocket  into  which  a  hollow 
revolving  plug  is  fitted  (Fig.  16).  This  plug  is  open 
at  one  end  so  as  to  accommodate  the  nozzle  of  a  Record 
syringe  (the  plug  may  be  made  to  fit  any  other  form 
of  syringe  desired ) ,  but  is  closed  at  its  other  end,  the 
point  of  exit  being  in  one  side  so  as  to  correspond 
to  the  openings  of  the  two  arms  of  the  U  into  the  cen- 
tral pocket.  The  distal  ends  of  the  arms,  then,  are 
attached  to  six  inches  (or  more)  of  rubber  tubing 
each  of  which  is  in  turn  attached  to  the  needles  which 


IVIETHODS  OF  TRANSFUSION  125 

have  been  placed  in  the  donor's  and  the  recipient's 
vessels.  ^  A  circuit  having  been  completed  in  this  man- 
ner, blood  is  withdrawn  by  means  of  a  syringe  from 
the  donor,  and  the  plug  is  gently  rotated  for  a  half 
circle  until  its  lateral  opening  faces  the  opening  of  that 
arm  of  the  U  leading  to  the  recipient's  vein,  where- 
upon the  syringe  is  emptied/  Reverse  rotation  brings 
the  plug's  opening  into  apposition  with  the  intake 
tube,  whereupon  the  syringe  is  again  filled  only  to  be 
promptly  emptied  into  the  recipient  by  a  half  rotation 
of  the  plug  similar  to  the  first  movement.  In  other 
words,  the  syringe  draws  up  blood  from  an  intake 
tube  and  empties  it  into  an  outgoing  tube,  the  rotation 
plug  acting  as  an  intermediary  between  the  two  tubes. 
A  small  metal  ball  attached  to  the  plug  facilitates 
its  rotation,  and  another  metal  pin  prevents  its  rotat- 
ing more  than  a  half  circle  by  working  in  a  specially 
constructed  slot.  Fin*thermore,  the  plug  is  ground 
into  its  pocket,   and,   though  easily  removable,   fits 

^  These  needles  may  be  either  sharp  or  blunt,  and  obtura- 
tors go  with  each  set.  By  this  means,  as  soon  as  the  needle  is 
placed  in  the  vein  its  lumen  is  closed  by  its  obturator.  All 
danger  of  clotting  is  obviated.  When  needles  have  been 
placed  in  both  patient's  and  recipient's  veins,  obturators  are 
removed  and  needles  are  attached  to  the  tubing  of  the  U  tube. 

^  It  is  unnecessary  to  paraffin  or  coat  with  albolene  any 
part  of  the  apparatus. 


126 


BLOOD  TRANSFUSION 


so  perfectly  as  to  prevent  entrance  of  air  into  the 
syringes.    Worthy  of  note,  too,  is  the  fact  that  when 


Fig.   1G — Author's  U  tube. 


the  lateral  opening  of  the  plug  is  "  set "  for  one  arm 
of  the  U,  the  other  arm  is  effectually  blocked,  thus 
preventing  any  leakage. 


METHODS  OF  TRANSFUSION  127 

In  this  manner  successive  syringefuls  of  blood  may 
be  withdrawn  from  the  donor  and  emptied  into  the 
recipient  with  accm*acy,  precision  and  rapidity.  iVnd 
inasmuch  as  no  sjTinge  should  ever  be  refilled  more 
than  tw^o  or  three  times  without  cleansing,  it  is  quite 
simple  as  well  as  advisable  to  wash  a  few  cubic  centi- 
metres of  salt  solution  into  each  arm  of  the  U  as  each 
fresh  syringe  is  taken  up.  Thus  clotting  is  avoided. 
Should,  however,  a  clot  arise  or  should  it  be  necessary 
for  any  reason  to  discontinue  the  transfusion  tem- 
porarily, the  entire  apparatus  may  be  disconnected, 
washed  out  and  held  ready  for  resuming  the  operation." 
Kimptox-Browx  Method  as  Modified  by  Beth  Vincent 

"  The  results  obtained  by  the  transfusion  of  blood 
are  probably  less  dependent  upon  the  particular  method 
employed  than  upon  any  other  factor  pertaining  to 
the  subject.  The  indications  for  a  transfusion  and 
the  selection  of  the  donor  are  more  important  than  the 
technic  of  the  operation.  The  therapeutic  value  of  the 
blood  is  the  same  whether  transferred  by  the  citrate 
method  as  described  bv  Weil  and  Lewisohn,  with  the 
glass  cylinders  of  Kimpton  and  Brown,  the  pipette- 
cannular  apparatus  of  Satterlee  and  Hooker,  or  by 
the  syringe  method  of  Lindeman.  For  this  reason 
each  surgeon  should  familiarize  himself  with  the 
method  which  suits  his  own  needs.  The  following 
method  has  been  useful  to  me  and  may  meet  the  re- 
quirements of  other  operators. 


128  BLOOD  TRANSFUSION 

For  the  past  three  years  I  have  used  a  glass  tube 
or  flask  with  a  paraffin  coating  which  inhibits  the 
coagulation  of  blood  and  allows  ample  time  to  transfer 
it  from  donor  to  recipient.  The  tube  resembles  in 
principle  and  differs  in  shape  from  the  cylinders  de- 
scribed by  Kimpton  and  Brown  and  the  pipette  of 
Satterlee  and  Hooker.  This  method  is  easy  and  prac- 
tical and  requires  a  skin  incision  to  expose  the  vein  in 
both  donor  and  recipient  which  is  not  necessary  in 
many  cases. 

Recently  I  have  modified  the  tube  so  tliat  it  can 
be  used  with  a  needle  of  special  design  which  obviates 
the  skin  incision  on  individuals  with  suitable  veins. 
After  a  year's  experience  with  the  needle  and  the  tube 
at  the  Massachusetts  General  Hospital  and  in  my 
private  work  I  find  that  this  is  the  case  with  the  donor, 
at  least,  in  a  large  percentage  of  transfusions. 

The  tube  is  a  cylinder  with  a  capacity  of  309  c.c, 
the  upper  end  of  which  is  closed  with  a  rubber  cork. 
About  3  cm.  below  the  end  is  a  side  opening  where 
connection  is  made  with  a  bulb  syringe  which  is  used 
to  express  the  contents  of  the  tube.  The  lower  end 
of  the  cylinder  terminates  in  a  glass  tip,  through  which 
the  blood  enters  and  leav^es  the  tube.  About  2  cm. 
above  the  end  of  the  tip  is  a  ground-glass  joint  by 
means  of  which  a  tight  connection  can  be  made  with 
the  needle. 


METHODS  OF  TRANSFUSION  129 

The  needle  is  6  cm.  long  and  consists  of  a  shaft 
and  a  socket  of  about  equal  length.  The  socket,  which 
is  the  special  feature  of  the  needle,  is  made  of  an 
unusual  depth  so  that  there  is  no  contact  between  the 
needle  and  that  portion  of  the  glass  tip  which  pro- 
jects into  the  socket  below  the  ground-glass  joint. 
The  needle  is  made  in  two  sizes,  number  14  and  16 
gauge.    I  find  that  I  use  the  larger  size  in  most  cases. 

PREPARATION  OF  TUBE  AND  NEEDLE 

"  The  tubes  are  cleansed  with  hot  water,  wrapped 
in  a  towel  with  the  cork  and  a  short  piece  of  rubber 
tubing  and  sterilized  and  dried  in  the  autoclave.  The 
process  of  coating  the  tubes  with  paraffin  is  then  car- 
ried out  under  aseptic  conditions.  I  have  used  54  per 
cent,  paraffin  and  various  mixtures  of  stearin,  paraffin 
and  vaseline  for  coating  and  find  that  a  commercial 
article  sold  under  the  name  of  "  parowax  "  sei'v^es  all 
practical  purposes. 

The  paraffin  which  has  been  melted  and  sterilized 
in  a  metal  dish  is  aspirated  into  the  lower  end  of  the 
tube  and  the  outlets  are  covered  with  pads  of  gauze, 
while  the  tube  is  turned  to  make  the  wax  run  over 
all  the  inner  surface.  The  excess  of  paraffin  is  allowed 
to  run  out  at  the  tip,  leaving  a  small  amount  in  the 
tube  to  cover  the  cork  when  the  tube  is  placed  upon 
end  to  cool.     This  forms  a  disk  of  wax  which  makes 

9 


130  BLOOD  TRANSFUSION 

the  cork  air-tight,  a  condition  which  is  essential  to 
the  proper  use  of  the  tube.  As  the  tube  cools  a  coating 
of  paraffin  appears  on  the  inner  surface.  One  sliould 
make  sure  that  this  covering  is  uniform  and  that  the 
outlets  are  patent  before  the  tubes  are  done  up  in 
sterile  towels  and  put  aside  for  future  use. 

The  needles  are  cleansed,  dried,  and  heated  until 
sterile  in  a  dish  of  melted  paraffin.  With  sterile  for- 
ceps a  needle  is  then  taken  from  the  dish  and  the 
excess  of  wax  is  removed  by  shaking  or  by  blowing 
air  through  the  needle  with  a  bulb  syringe  during  the 
process  of  cooling  to  prevent  the  formation  of  a  plug 
of  wax  in  the  lumen.  The  needles  are  then  sterile 
and  coated  and  can  be  kept  in  a  sterile  box  until 
needed. 

This  process  of  coating  the  tubes  and  needles  re- 
quires some  practice  and  is  bothersome  to  the  sur- 
geon. It  is  one  of  the  disadvantages  of  the  method, 
but  the  work  can  be  delegated  to  any  intelligent  nurse. 
Prepared  and  put  up  in  this  way  the  needles  and 
tubes  may  be  kept  indefinitely  and  are  always  ready 
for  immediate  use.  * 

USE   OF   XEEDLE   AND   TUBE 

**  The  method  of  using  the  needle  and  tube  varies 
with  the  case  to  be  transfused  and  the  experience  of 
the  operator.  The  tube  should  be  used  without  the 
needle  in  cases  in  which  the  veins  of  both  donor  and 


METHODS  OF  TRANSFUSION  131 

recipient  are  small  or  hidden  by  a  heavy  layer  of  sub- 
cutaneous fat,  or  when  the  surgeon  lacks  practice  in 
vein-puncture  and  is  unable  to  enter  the  vein  without 
causing  a  hasmatoma.  Under  these  circumstances  it 
is  advisable  to  expose  and  open  the  vein  through  a  skin 
incision  and  insert  the  tip  of  the  tube  directly  into 
the  vein  as  described  by  Kimpton  and  Brown.  The 
blood  is  usually  taken  from  one  of  the  larger  veins  in 
•  the  donor's  elbow ;  while  any  vein  in  the  arm  or  leg 
which  will  admit  the  glass  tip  can  be  used  in  trans- 
ferring the  blood  to  the  recipient. 

In  most  transfusions  the  veins  of  the  donor  are 
large  and  easy  to  puncture  with  the  needle,  while  the 
veins  of  an  anaemic  recipient  are  apt  to  be  small  and 
hard  to  locate.  For  this  reason  it  is  usually  advis- 
able to  take  the  blood  from  the  donor  into  the  tube  by 
means  of  the  needle,  then  disconnect  the  needle  from 
the  tube  and  inject  the  blood  into  the  recipient  through 
the  glass  tip  which  is  inserted  directly  into  a  small  vein 
previously  exposed  by  skin  incision. 

Fig.  17  shows  the  manner  of  using  the  needle  and 
tube  to  take  the  blood  from  a  vein  at  the  donor's  elbow. 
The  arm  is  prepared  with  iodine  and  a  small  amount 
of  novocaine  is  injected  into  the  skin  over  the  selected 
vein  which  is  made  prominent  by  a  tom-niquet  applied 
above  the  elbow.  The  application  of  the  tourniquet 
is  important;  it  should  be  placed  directly  on  the  skin 


132 


BLOOD  TRANSFUSION 


and  adjusted  by  the  operator  so  as  to  secure  the  maxi- 
num  venous  tension  without  stopping  the  arterial  flow. 


Fig.   17. — Shows  use  of  needle  to  take  blood  from  vein  at  the  elbow.    {Surg.,  Gyne.  and 
Obstet.,  November  5,  1916,  vol.  xxiii. 


The  needle  is  connected  to  the  tube  before  making 
the  puncture  and  inserted  into  the  vein  toward  the 
wrist.    As  soon  as  the  vein  is  entered  the  blood  appears 


METHODS  OF  TRANSFUSION  133 

at  the  bottom  of  the  tube  and  steadily  rises  to  the 
top  by  virtue  of  the  pressure  in  the  vein.  The  rate 
of  flow  is  increased  if  the  donor  "  works  the  fist " 
during  the  procedure.  When  the  tube  is  filled,  which 
usually  takes  thi*ee  or  four  minutes,  the  flow  is  checked 
by  releasing  the  toui'niquet.  This  should  be  done 
before  the  needle  is  removed  to  avoid  the  formation 
of  a  h^ematoma.  As  the  needle,  still  attached  to  the 
tube,  is  withdrawn  pressure  is  made  over  the  vein  at 
the  site  of  the  puncture.  The  needle  is  then  discon- 
nected from  the  tube  and  rinsed  in  cold  salt  solution. 
During  this  time  the  tube  is  kept  in  a  horizontal  posi- 
tion with  the  tip  up  to  prevent  the  escape  of  blood. 
To  complete  the  transfer,  place  the  finger  over  the 
upper  opening  of  the  tube  to  control  the  flow  of  blood, 
depress  the  lower  end  and  insert  the  tip  into  the  vein 
of  the  recipient. 

The  average  transfusion  requires  at  least  600  c.c. 
of  blood.  In  most  cases,  if  a  hsematoma  does  not 
form  around  the  vein,  it  is  possible  to  take  two  and 
sometimes  three  tubes  of  blood  from  the  same  vein 
by  reinserting  the  needle  through  the  original  skin 
puncture.  It  is  not  necessary  to  use  a  fresh  tube 
and  needle  for  each  transfer  of  blood.  If  cleansed 
immediately  with  cold  salt  solution  they  may  be  em- 
ployed a  second  or  even  a  third  time  in  the  same 
transfusion.     A  single  tube  and  two  needles  usually 


134  BLOOD  TRANSFUSION 

suffice  for  a  transfusion,  although  one  should  always 
be  prepared  with  at  least  two  coated  tubes  and  extra 
needles. 

The  combination  of  needle  puncture  for  the  donor 
and  incision  for  the  recipient  is  the  practical  method 
in  most  transfusions,  but  under  certain  circumstances 
it  is  possible  to  use  the  needle  on  both  the  donor  and 
the  recipient.  In  such  cases  after  the  tube  has  been 
filled  with  blood  from  the  donor  as  already  described 
a  needle  is  inserted  into  the  median  basilic  or  median 
cephalic  vein  of  the  recipient  made  prominent  by  a 
tourniquet  above  the  elbow.  As  soon  as  blood  flows 
from  the  needle  the  tourniquet  is  loosened,  the  tube, 
filled  with  blood,  is  connected  with  the  needle  and  the 
contents  expressed  by  means  of  the  syringe. 

This  needle  and  tube  method  without  incision  ap- 
plies especially  well  to  the  infant  with  an  open  ante- 
rior fontanelle  where  the  blood  is  injected  into  the 
superior  longitudinal  sinus  as  suggested  by  Helmholz. 

In  my  last  seven  cases  of  hemorrhagic  disease  of 
the  newborn  I  have  employed  this  method  with  very 
satisfactory"  results.  The  blood  is  taken  by  means  of 
the  needle  from  an  elbow  vein  of  the  father  who 
usually  serves  as  the  donor.  One-half  a  tube,  or  150 
c.c.  of  blood,  is  sufficient,  as  the  amount  required 
to  transfuse  these  cases  varies  from  90  to  120  c.c. 
The   infant  is  placed  at   the  end   of  a  table   with 


METHODS  OF  TRANSFUSION 


135 


the  head  on  one  side,  as  shown  in  Fig.  18,  and  held 
firmly  in  this  position  by  an  assistant.  The  needle  is 
inserted  at  the  posterior  angle  of  the  anterior  fonta- 


Fio.   18. — Shows  position  of  infant's  head  and  point  at  which  the  injection  of  blood  is 
made  into  the  longitudinal  sinus. 


nelle  exactly  in  line  with  the  sagittal  suture.  The 
sinus  is  just  beneath  the  skin  and  dura  and  large 
enough  at  this  point  to  be  located  easily  even  in  a 


P 


136  BLOOD  TRANSFUSION 

new-born  infant.  As  soon  as  the  needle  enters  the 
sinus  the  fact  is  revealed  by  the  flow  of  blood  from 
the  outer  end.  The  needle  is  then  held  firmly  in  place 
while  connection  is  made  with  the  tube  and  the  blood 
is  slowly  injected.  The  blood  must  be  injected  slowly 
to  avoid  a  too  rapid  increase  of  intracranial  pressure. 
In  two  of  my  cases  this  caused  vomiting  and  disturbed 
respiration  which  corrected  itself  as  soon  as  the  flow 
of  blood  was  checked  temporarily.  Air  pressure  in 
the  tube  should  be  released  by  detaching  the  syringe 
before  the  needle  is  withdrawn.  There  is  no  bleeding 
of  any  amount  from  the  sinus  even  if  the  puncture  has 
been  made  with  a  fairly  large  needle. 

The  chief  disadvantage  of  this  method  of  trans- 
fusion lies  in  the  preparation  of  the  needles  and  tubes 
but  this  process  is  not  difficult  and  may  be  done  in 
advance.  The  coated  needles  and  tubes  can  be  kept 
indefinitely  and  are  always  ready  for  immediate  use. 
In  practice  the  method  is  certain  and  flexible.  The 
combination  of  needle  and  tube  allows  the  surgeon  to 
make  a  choice  of  procedures  to  suit  his  own  operative 
experience  and  the  need  of  the  individual  case.  The 
tube  with  open  incision  is  a  sure  method  for  any  trans- 
fusion and  under  favorable  conditions  the  use  of 
the  needle  with  the  tube  materially  simplifies  the 
operation." 


METHODS  OF  TRANSFUSION  137 

Action  of  Sodium  Citrate 

Before  giving  the  details  of  Lewisohn's  method  of 
using  sodiuni  citrate  for  purposes  of  blood  transfusion, 
an  understanding  concerning  the  action  of  the  drug 
in  the  body  seems  advisable.  To  this  end  the  recent 
investigations  of  Salant  and  Wise  throw  much  light 
on  the  subj  ect  and  come  at  a  peculiarly  fortunate  time. 
A  summary  of  their  views  is  as  follows : 

1.  Sodium  citrate  is  gotten  rid  of  by  the  body  in 
two  ways:  (a)  oxidation  by  the  tissues  (not  including 
the  blood)  into  carbon  dioxide  and  water  as  shown 
by  Batteli  and  Stein  and  (h)  through  the  kidneys. 
Apparently  most  of  it  is  oxidized  but  a  considerable 
amount  (possibly  30  to  40  per  cent.)  is  eliminated  by 
the  kidneys,  the  urine  being  made  alkaline  by  the  drug. 

2.  It  disappears  rapidly  from  the  circulation  after 
intravenous  injection  into  cats  and  dogs.  For  ex- 
ample, 100  mg.  of  sodium  citrate  per  kilo  were  in- 
jected into  the  femoral  vein  of  a  dog  and  about  60  to 
70  per  cent,  disappeared  in  twenty  seconds,  while 
10  to  20  per  cent,  of  the  remainder  disappeared  during 
the  next  five  to  ten  minutes. 

3.  The  oxidation  and  elimination  are  retarded 
when  the  doses  are  repeated  and  are  probably  much 
slower  when  large  doses  are  given  at  frequent 
intervals. 


138  BLOOD  TRANSFUSION 

4.  Large  doses  given  subcutaneously  showed 
cumulative  action. 

5.  The  toxicity  of  sodium  citrate  when  given  in- 
travenously depends  to  a  large  degree  upon  the  rate 
of  injection.  This  was  proved  by  injecting  a  fatal 
dose  rapidly  and  then  giving  the  same  dose  to  another 
animal  very  slowly.  If  the  time  of  injection  was 
extended  over  a  really  considerable  period,  such  as 
two  or  three  hours,  a  much  larger  dose  could  be  with- 
stood than  had  proved  fatal  in  the  first  instance. 

6.  The  toxicity  of  sodium  citrate,  aside  from  the 
rate  of  injection,  depends  upon  the  rate  of  its  oxida- 
tion in  the  body,  being  more  toxic  for  animals  in  which 
larger  quantities  are  eliminated  unchanged. 

7.  No  after  effects  at  all  were  observed  from  th6 
use  of  sodium  citrate.  Xeither  sugar  nor  albumin 
was  present  in  the  urine  which  was  examined  for  sev- 
eral days  after  toxic  doses  were  administered.  Symp- 
toms developed  rapidly,  especially  after  large  doses, 
and  ended  in  recovery  or  death  within  a  few  hours. 
The  action  of  the  drug  is  therefore  acute  only. 

8.  Salant  and  Wise  carried  out  all  their  investiga- 
tions on  animals,  but  Lewisohn,  whose  preliminary 
work  was  done  with  animals,  determined  that  large 
amounts  of  a  0.2  per  cent,  solution  of  sodium  citrate 
could  be  injected  into  a  human  without  the  slightest 
iharm,  and  since  citrate  in  this  dilution  will  prevent 


METHODS  OF  TRANSFUSION  139 

blood  from  clotting  for  two  to  three  days,  it  is  a  most 
advantageous  agent. 

Lewisohn's  Method  of  Sodium  Citrate  Transfusion 
*'  The  donor  is  put  on  a  table,  a  tourniquet  applied 
to  the  arm,  and  the  vein  punctured  with  a  cannula. 
The  blood  is  received  in  a  sterile  graduated  glass 
jar  (500  cm.)  containing  25  c.c.  of  a  2  per  cent,  sterile 
solution  of  sodium  citrate  at  the  bottom.  While  the 
blood  is  running  into  the  glass  receptacle,  it  is  well 
mixed  with  the  citrate  solution  by  means  of  a  glass 
rod.  After  250  c.c.  of  blood  have  been  taken  another 
25  c.c.  of  citrate  solution  are  added.'  If  less  than 
500  c.c.  of  blood  are  taken  (i.e.,  in  infants) ,  the  amount 
of  citrate  solution  added  to  the  blood  is  reduced  ac- 
cordingly. In  cases  where  we  expect  to  take  more 
than  500  cubic  centimetres  of  blood  we  have  another 
glass  container  (500  cm.)  ready  to  be  used  in  exactly 
the  same  manner.  The  glass  jar  containing  the  blood 
is  then  put  aside  and  covered  with  a  towel  to  safeguard 
against  contamination.    I  have  not  found  it  necessary 

^  Fifty  cubic  centimetres  of  a  2  per  cent,  solution  of  so- 
dium citrate  make  a  final  dilution  of  0.2  per  cent,  citrate 
when  added  to  500  c.c.  of  blood.  But,  since  it  is  always 
advisable  to  have  an  excess  of  citrate,  450  c.c.  of  blood  is  a 
better  amount  to  take  than  500  c.c.  to  50  c.c.  of  citrate.  The 
clinical  dilution  therefore  really  amounts  to  about  0.25  per 
cent,  rather  than  0.2  per  cent. 


140  BLOOD  TRANSFUSION 

to  immerse  it  in  hot  water  or  surround  the  jar  with 
an  asbestos  covering.  The  blood  is  then  taken  either 
into  the  recipient's  room  or  the  recipient  is  brought 
into  the  operating  room.  I  consider  it  a  great  ad- 
vantage that  this  method  does  not  require  donor  and 
recipient  to  be  in  the  same  room;  this  lessens  the 
psychical  shock  of  the  whole  procedure  for  the  pa- 
tient. In  fact,  the  donor's  blood  may  be  collected 
in  the  laboratory  or  office  and  carried  to  the  patient's 
bedside. 

Another  very  great  advantage  of  the  citrate 
method  is  that  as  there  is  no  connection  between  the 
donor  and  recipient,  the  donor  is  safeguarded  against 
contagion  of  any  disease  or  infection  which  the  patient 
may  have. 

The  recipient's  vein  is  then  punctured  or  exposed 
by  a  small  incision;  the  cannula  is  introduced  and 
attached  to  a  salvarsan  flask  or  a  glass  funnel.  It  is 
advisable  to  fill  the  rubber  tubing  connection  between 
flask  and  cannula  with  some  saline  solution,  so  as  to 
prevent  air  from  getting  into  the  circulation.  After 
the  connection  is  made  the  blood  is  poured  into  the 
salvarsan  apparatus.  In  order  to  prevent  sudden 
overloading  of  the  circulation  it  is  advisable  (espe- 
cially in  larger  transfusions)  to  stop  the  flow  of  blood 
from  time  to  time  by  compressing  the  rubber  tubing. 
After  the  blood  has  been  injected  the  cannula  is  re- 


METHODS  OF  TRANSFUSION  141 

moved  and  the  transfusion  is  thus  ended.  The  whole 
procedure  can  be  perf  oraied  with  the  greatest  ease  and 
without  any  hurry,  because  the  citrated  blood,  as 
we  have  seen  above,  can  be  kept  for  two  or  three  days 
in  the  glass  jar  without  danger  of  clotting." 

DISCUSSION    AS    TO    THE    MERITS   OF    CITRATED    BLOOD    FOR    PUR- 
POSES   OF    TRANSFUSION    AS    COMPARED    TO    WHOLE, 
UNTREATED    BLOOD 

While  it  is  true  that  citrated  blood  will  remain 
unclotted  for  forty-eight  hours  or  more,  there  is  some 
doubt  as  to  the  advisability  of  using  it  for  transfusion 
pm*poses  after  it  has  been  outside  of  the  body  any 
great  length  of  time.  Investigations  concerning  this 
matter  are  greatly  to  be  desired,  since  it  is  possible  that 
the  cells  may  undergo  some  physiological  or  chemical 
change  that  would  render  them  harmful  when  injected 
into  the  living  blood  stream — or  at  least  unfit  for 
carrying  out  the  purposes  for  which  they  were  in- 
tended. In  a  personal  communication  some  months 
ago,  Lewisohn  rather  advised  against  keeping  the 
blood  more  than  24  hours.  I  have  used  it  after  a 
three-hour  interval  and  would  not  hesitate  to  use  it 
after  six  hours,  but  until  more  definite  information  is 
forthcoming,  it  seems  to  me  best  to  maintain  a  con- 
servative attitude.  In  fact,  I  can  see  little  reason  for 
keeping  blood  in  bulk.  Where  the  patient  lives  at  a 
distance  from  the  hospital  or  perhaps  in  a  neighboring 


142  BLOOD  TRANSFUSION 

city  it  would  seem  far  safer  to  take  the  donor  to  the 
home  instead  of  collecting  the  blood  and  carrj^ing  it 
in  flasks;  and  where  small,  broken  doses  of  blood  are 
indicated,  it  is  safer  and  simpler  to  take  the  amounts 
of  blood  from  the  donor  as  they  are  required  rather 
than  ^^athdraw  the  entire  quantity  desired  at  one  time 
and  be  compelled  to  keep  it. 

So  far  as  can  be  determined  there  seems  to  be 
little  difference  between  the  therapeutic  action  of 
whole  blood  and  citrated  blood,  although  there  sliould 
be  a  vast  difference  from  a  purely  theoretical  view- 
point. Since  sodium  citrate  definitely  inhibits  l)lood 
coagulation  outside  the  body,  it  would  certainly  seem 
that  its  intravenous  injection  should  raise  the  coagu- 
lation time  of  the  blood.  If  this  were  true,  its  use 
would  be  contraindicated  in  all  forms  of  the  hemor- 
rhagic group  of  diseases  and  in  the  presence  of  active 
bleeding.  The  reverse,  however,  happens  to  be  true. 
Instead  of  raising  the  coagulation  time,  according  to 
Lewisohn  and  Weil,  citrated  blood  lowers  it  for  a  time, 
after  which  coagulation  time  returns  to  nonnal.  I 
have  made  no  personal  investigations  on  this  point,  but 
have  proved  by  repeated  clinical  trial  that  its  use  in 
all  forms  of  bleeding  is  attended  with  the  same  happy 
results  as  is  that  of  whole  untreated  blood.  For  ex- 
ample, a  500-c.c.  transfusion  of  citrated  blood  caused 
an  immediate  and  permanent  cessation  of  a  profuse, 


METHODS  OF  TRANSFUSION  143 

active  hemorrhage  from  a  gastric  ulcer.  A  55-c.c. 
dose  of  citrated  blood  brought  about  an  equally  satis- 
factory termination  of  bleeding  in  an  infant  one  week 
old,  who  had  had  a  family  history  of  haemophilia  and 
took  up  the  burden  himself  when  he  was  circumcised. 
His  condition  was  rapidly  approaching  the  danger 
line.  In  another  case,  an  obscure  purpura,  where  a 
long  series  of  transfusions  were  given,  both  of  whole 
blood  and  citrated  blood,  the  latter  variety  exerted 
e(jually  as  much  influence  on  blood  coagulation  as  the 
whole  blood ;  neither  brought  about  an  entire  stoppage 
although  both  caused  a  marked  improvement.  The 
results  in  other  instances  only  reinforce  the  above  con- 
clusion. It  seems  paradoxical.  I  do  not  understand 
it,  and  Dr.  Howell,  to  whom  I  have  gone  for  an  ex- 
planation, can  hardly  believe  it  possible  that  such  is 
the  case,  but  these  are  facts  which  have  been  repeated 
over  and  over  again  and  always  with  the  same  result. 

But  there  is  one  diiFerence  between  a  citrate  trans- 
fusion and  one  in  which  whole  untreated  blood  is  used 
that  cannot  be  passed  over — -a  post-transfusion  reac- 
tion, as  manifested  by  a  chill  and  fever,  follows  the 
citrate  transfusion  far  more  frequently  than  one  with 
whole  blood,  and  in  cases  where  donor's  and  recipient's 
bloods  match  perfectly  by  eveiy  known  test.  Indeed, 
it  is  most  unusual  in  my  experience  to  have  the 
slightest  reaction  after  the  whole  blood  transfusion 


144  BLOOD  TRANSFUSION 

with  perfectly  matched  hloods — even  a  rise  of  tem- 
perature of  more  tlian  a  degree  or  two  is  unusual. 
With  the  citrate  blood,  a  violent  chill  and  fever  up 
to  103°  or  105°  is  to  be  expected  about  20  minutes 
after  transfusion  in  about  one  out  of  every  three  or  four 
cases  and  minor  grades  of  the  same  sort  occur  even  more 
frequently.  This  is  most  distressing  to  the  patient 
and  is  unfortunate  but  it  is  of  no  consequence  so 
far  as  the  ultimate  result  is  concerned,  since  it  is  un- 
accompanied by  any  blood  destruction  such  as  would 
be  manifested  by  a  hemoglobinuria.  In  the  light  of 
Salant  and  Wise's  w^ork  it  may  be  due  to  the  too  rapid 
introduction  of  the  citrated  blood,  but  this  is  doubtful, 
since  it  has  occurred  after  the  slowest  kind  of  trans- 
fusion and  after  the  most  elaborate  care  to  avoid  it. 
It  is  of  citrate  origin  surely,  but  future  investigation 
must  reveal  its  true  nature.  One  of  the  inexplicable 
features  of  this  reaction  is  that  its  occurrence  or  non- 
occurrence cannot  be  predicted.  For  example,  I  had 
occasion  to  do  two  transfusions  on  one  patient  and 
used  the  same  perfectly  matched  donor  for  both.  The 
interval  was  several  weeks,  the  exact  technic  was  used 
each  time,  the  amounts  of  blood  injected  were  identi- 
cal and  the  quantity  and  strength  of  the  citrate  were 
the  same.  Not  the  slightest  reaction  followed  the  first 
transfusion,  but  a  most  distressing  one  followed  the 
second,  and  great  benefit  accrued  from  both. 


METHODS  OF  TRANSFUSION  145 

It  is  possible,  even  probable,  that  these  reactions 
will  be  fathomed  and  eliminated,  but  since  they  are 
not  actually  harmful,  and  since  the  citrate  method 
of  transfusion  has  so  many  obvious  advantages  over 
all  other  methods,  it  seems  to  me,  after  careful  com- 
parison, to  be  the  present  method  of  election. 

REFERENCES 

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Bemheim,  B.  M. :  "  Surgery  of  the  Vascular  System."  J.  B. 
Lippincott  Company,  1913. 

Bemheim,  B.  M. :  "  An  Emergency  Cannula."  Jouriwl  of 
A.  M.  A.,  April  6,  1912. 

Bemheim,  B.  M. :  "A  Simple  Instrument  for  the  Indirect 
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Brem,  W.  V. :  "  Blood  Transfusion  with  Special  Reference  to 
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Crile,  G.  W. :  "  Hemorrhage  and  Transfusion."  Appleton 
and  Company,  1909. 

Curtis,  A.  H.,  and  David,  V.  C. :  *  Transfusion  of  Blood  by 
a  New  Method."  J.  A.  M.  A.,  January  7,  1911. 

Elsberg,  C.  A. :  "A  Simple  Canula  for  the  Direct  Transfu- 
sion of  Blood."    J.  A.M.  A.,  1909,  vol.  Hi,  p.  887. 

Helmholz,  H.  F. :  "  The  Longitudinal  Sinus  as  the  Place 
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and  Injections,  including  Transfusion."  Am.  Jour.  Dis- 
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10 


146  BLOOD  TRANSFUSION 

Kimpton,  A.  R.,  and  Brown,  J.  H. :  "A  New  and  Simple 

Method  of  Transfusion."  J.  A.  M.  A.,  July  12,  1913, 

vol.  Ixi,  pp.  117  and  118. 
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Blood  Transfusion."      Medical  Record,   January   23, 

1915,  p.  141. 
Lewifeohn,  R. :  "  Blood  Transfusion  by  the  Citrate  Method." 

Surg.,  Gyne.  and  Obstet.,  July,  1915,  pp.  37-47. 
Lewisohn,  R. :  "  The  Importance  of  the  Proper  Dosage  of 

Sodium  Citrate  in  Blood  Transfusion."  Annals  of  Sur- 
gery, November,  1916,  vol.  Ixiv,  No.  5. 
Libman,  E.,  and  Ottenberg,  R. : "  A  Practical  Method  for 

Determining  the  Amount  of  Blood  Passing  Over  During 

Direct  Transfusion."  J.  A.  M.  A.,  March  7,  1914,  vol. 

Ixii,  pp.  764-767. 
Lindeman,    Edward :     "  Simple    Syringe    Transfusion    with 

Special   Cannulas."   American  Journal  Dis.   Children, 

July,  1913,  p.  28. 
Satterlee,  H.  S.,  and  Hooker,  R.  S. :   "  Transfusion  of  Blood 

with  Special  Reference  to  the  Use  of  Anticoagulants." 

J.  A.  M,  A.,  February  26,  1916,  vol.  Ixvi,  pp.  618-624. 
Salant,  W.,  and  Wise,  L.  E. :  "  The  Action  of  Sodium  Citrate 

and  Its  Decomposition  in  the  Body."     The  Journal  of 

Biological  Chemistry,  vol.  xxviii,  December,  1916. 
Unger,  L.  J. :  "A  New  Method  of  Syringe  Transfusion." 

J.  A.M.  A.,  1915,  Ixiv,  p.  582. 
Vincent,  Beth :  "  Blood  Transfusion   with  Paraffin  Coated 

Needles    and    Tubes."     Surg.,    Gyne.    and   Obstetrics, 

November,  1916. 
Weil,  R. :  "Sodium  Citrate  in  the  Transfusion  of  Blood." 

J.  A.  M.  A.,  January  30,  1915,  vol.  Ixiv,  pp.  425-426. 


CHAPTER  VIII 

TRANSFUSION  FOR  ACUTE  HEMORRHAGE  AND 
SHOCK.  ACCIDENTAL  GASTRIC  ULCER.  POST- 
OPERATIVE. POSTPARTUM.  PLACENTA  PR.E- 
VL4.  EXTRA-UTERINE  PREGNANCY.  TYPHOID 
FEVER 

According  to  BischofF,  the  blood  of  a  human 
makes  up  about  7.4  per  cent,  of  his  total  body  weight 
and  experiments  on  animals  seem  to  indicate  that  a 
healthy  individual  could  lose  half  of  this  amount  and 
still  recover  without  serious  difficulty.  With  these 
figures  clearly  in  mind,  one  might  think  it  ought  to 
be  possible  to  gauge  the  extent  of  a  hemorrhage  and 
tell  accurately  when  the  borderline  has  been  reached. 
And  so  it  would  be,  perhaps,  were  it  not  for  the  un- 
known and  unfathomable  human  factor  that  plays 
such  a  tremendous  role  in  all  illness.  We  do  not 
know  how  much  blood  an  individual  can  lose  with 
safety  because  so  many  features  enter  into  any  com- 
putation that  it  is  well-nigh  impossible  to  take  them 
all  into  account.  Common  report  has  it  that  the 
mother  in  child-birth  can  lose  tremendous  amounts  of 
blood  with  impunity;  certainly  mothers  do  lose  great 

147 


148  BLOOD  TRANSFUSION 

volumes  and  obstetricians,  more  than  any  other  set  of 
medical  men,  can  sit  idly  by  and  watch  a  blood  flow 
from  the  parturient  woman  that  would  appall  his 
physician  or  surgeon  brother.  Perhaps  the  woman 
at  term  has  more  blood  than  at  other  times,  more, 
possibly  than  her  own  body  could  use  after  her  uterus 
has  been  emptied — but  it  is  within  the  bounds  of  rea- 
son to  suppose  that  the  customary  post-partum  pros- 
tration might  be  less  profound  were  the  bleeding  at 
parturition  less  profuse. 

Whether  it  is  true  that  at  child-birth  more  blood 
can  be  lost  than  at  any  other  time,  or  whether  it  is 
not,  there  certainly  is  absent  at  this  time,  in  the  great 
majority  of  cases,  that  one  featiu*e  that  plays  the 
greatest  part  in  determining  how  great  or  how  little 
bleeding  can  be  withstood — the  psychic  element.  The 
woman  in  labor  is  fully  occupied  with  her  pains  and 
the  actual  physical  work  she  must  perform;  she  has 
neither  the  time  nor  inclination  to  worry  about  a  little 
thing  like  bleeding,  which,  even  when  it  does  come, 
she  never  sees.  Practically  always  it  occurs  when  she 
is  at  the  end  of  her  work,  so  tired  and  worn  out  that 
she  really  is  not  interested.  The  psychic  element  is 
totally  absent — perhaps  this  accounts  in  a  measure  for 
her  salvation. 

What,  then,  is  this  psychic  element?  I  confess  I 
do  not  know.     Shock  is  the  common  technical  term 


TRANSFUSION  FOR  ACUTE  CONDITIONS      149 

applied,  but  it  fails  utterly  to  explain  this  intangible 
complicating  factor  in  our  work.  In  certain  instances 
it  is  partly  compounded  of  fear,  fear  of  impending 
death,  but  to  claim  that  it  is  fear  in  every  case  would 
be  unfair  to  that  large  group  of  individuals,  who, 
against  overwhelming  odds,  display  an  inspiring  cour- 
age. There  is  no  proof,  in  fact,  in  the  assumption  that 
the  brave  withstand  blood  loss  better  than  the  faint- 
hearted, although  this  is  a  tempting  view  to  hold.  I 
have  often  seen  men,  in  whom  there  was  not  the 
slightest  fear  or  anxiety  as  to  the  outcome,  go  utterly 
to  pieces  at  a  trifling  hemorrhage,  and  I  recall  sev- 
eral instances  of  real  cowards  withstanding  consider- 
able loss.  If  a  man  has  been  caught  up  in  a  set  of  cog- 
wheels and  flung  around  and  around  and  has  come  out 
maimed  and  bleeding,  he  is  quite  naturally  upset;  his 
mental  equilibriimi  has  been  profoundly  deranged; 
that  is  quite  understandable.  But  the  man  who  has 
had  an  artery  severed  by  a  stray  bullet  or  an  acci- 
dental knife  wound  has  encountered  nothing  more  to 
shake  his  innermost  mental  workings  than  the  sight 
of  his  own  blood  pouring  out  of  his  vessels,  yet  the 
same  phenomenon  of  psychic  disturbance  may  be  en- 
countered in  him  as  was  encountered  in  his  mate  of 
the  cog-wheels — and  neither  may  have  had  any  fear 
in  the  least.  Certain  individuals  are  much  more 
affected  by  blood  loss  than  others ;  the  size,  age,  social 


150  BLOOD  TRANSFUSION 

status,  et  cetera,  have  little  or  nothing  to  do  with  the 
question.  Quite  naturally  any  accident  will  affect  a 
man  in  ill-health  more  seriously  than  his  robust  mate, 
but  that  the  big  husky  day  laborer  will  stand  an  acci- 
dental hemorrhage  better  than  the  under-nourished, 
anaemic-looking  clerk  can  never  be  predicted.  I  some- 
times think  it  all  depends  upon  the  brain  centres,  espe- 
cially the  centre  for  blood-pressm-e,  since  it  is  a  well- 
known  fact  that  certain  tissues  can  stand  severe  and 
prolonged  anaemia  much  better  than  others,  and  of 
these,  brain  tissue  is  by  far  the  most  susceptible.  The 
ordinar}'^  faint  is  an  illustration  of  the  dire  conse- 
quences of  even  temporary  depletion,  the  lowering  of 
the  head  of  the  bed  in  all  forms  of  fainting  and  bleed- 
ing being  but  the  mechanical  attempt  to  favor  the 
circulation  in  the  cranium.  Certain  it  is  that  the 
psychic  element,  call  it  shock  or  anything  else,  is  most 
intimately  linked  with  the  centre  for  blood-pressure, 
but  which  one  is  the  most  important  or  plays  the  pri- 
mary role  it  is  impossible  to  tell.  The  most  one  can 
say  is — given  a  profoundly  disturbed  psychic  base  in 
cases  of  bleeding,  a  falling  blood-pressure  will  result ; 
given  a  psychic  state  of  slight  disturbance,  a  stable, 
though  possibly  somewhat  fluttering,  blood-pressure 
will  be  found — while  a  rising  pressure  portends  a 
return  to  the  noi*mal  mental  state,  although  this  latter 
statement  can  be  put  just  the  other  way  around. 


TRANSFUSION  FOR  ACUTE  CONDITIONS      151 

namely  a  returning  equilibrium  will  be  accompanied 
by  a  rising  pressure.  Those  who  have  worked  in  the 
field  of  transfusion  will  best  understand  the  above 
discussion,  while  those  who  have  seen  isolated  cases  of 
hemorrhage  may  recognize  certain  phases  similar  to 
those  encountered  in  their  cases.  The  frantic  attempts 
of  relatives,  friends,  nurses  and  physicians  to  allay 
the  fears  of  the  injured  or  to  quiet  those  suddenly 
seized  with  desperate  illness,  the  white  lies  so  glibly 
told  to  the  dying  that  "All's  well,"  "  You're  picking 
up  wonderfully  well,"  are  our  pathetic  attempts  to 
combat  the  depressed  psychic  condition  which  we 
know  must  be  buoyed  and  lightened  if  restorative 
measures  are  to  be,  in  any  way,  successful. 

ACCIDENTAL  HEMORSAGE 

By  accidental  hemorrhage  is  understood  those 
bleedings  arising  from  wounds  inflicted  by  any  and 
all  means — industrial  accidents,  stab  wounds,  bullet 
wounds,  and  such.  Frequently,  actual  blood  loss  may 
not  be  so  gi-eat  as  to  cause  the  profound  prostration 
exhibited  by  the  patient,  but  investigation  will  reveal 
the  fact  that  in  many  such  cases  the  initial  hemor- 
rhage was  quite  sharp,  so  sharp  in  fact  that  it  seemed 
as  if  death  would  ensue  almost  immediately.  The 
patient  fainted  away — and  thereby  probably  saved 
his  own  life !   Rapid  depletion,  tremendous  abrupt  fall 


152  BLOOD  TRANSFUSION 

in  blood-pressure,  anaemia  of  the  brain,  syncope,  occa- 
sion a  slowing  of  the  blood  current  and  absolute  quiet 
of  the  patient,  which  more  than  anything  else  are  con- 
ducive to  clot  formation  at  the  site  of  the  bleeding. 
Were  it  not  for  this  sequence  of  events,  I  dare  say  the 
mortality  from  accidental  hemorrhages  would  be  more 
than  double  what  it  is  to-day.  Rapid  loss  of  even 
comparatively  small  amounts  of  blood  is  of  far  more 
serious  consequence  than  gradual  loss  of  greater 
amounts,  since  in  the  latter  case  opportunity  is 
afforded  the  vascular  apparatus  to  adjust  itself  to 
conditions. 

It  should  be  an  axiom  among  surgeons  never  to 
start  a  transfusion  in  accidental  or  other  hemorrhages 
without  first  having  controlled  the  original  source  of 
bleeding  if  possible.  Failure  to  do  this  merely  invites 
disaster,  by  pumping  in  and  pumping  out  at  the  same 
time.  There  may,  however,  be  instances  where  the 
condition  of  the  patient  is  so  precarious  as  to  preclude 
an  attempt  to  do  anything.  If  such  be  the  case,  the 
best  plan  is  to  start  the  transfusion,  and  have  every- 
thing in  readiness  to  seek  the  source  of  the  trouble  the 
moment  the  patient  picks  up  sufficiently  to  warrant 
such  an  attempt.  By  this  means,  many  lives  can  be 
saved  that  otherwise  would  be  lost.  Practically  none 
of  the  donor's  blood  will  be  lost,  since  it  requires  hardly 
more  than  100  or  150  c.c.  for  a  patient  to  pick  up 


TRANSFUSION  FOR  ACUTE  CONDITIONS      153 

sufficiently,  and  after  the  bleeding  point  is  caught  the 
transfusion  may  be  continued  to  its  logical  conclusion. 
Oftentimes  the  wound  is  of  such  nature  that  prolonged 
manipulations  are  necessarj^  to  secure  the  bleeding 
point  and  more  blood  may  be  lost  during  them,  in 
which  case  the  donor's  blood  had  better  be  conserved. 
This  can  only  be  done  by  an  interruption  of  the  trans- 
fusion from  time  to  time,  and  resuming  it  as  the 
patient's  condition  demands,  for  which  purpose  the 
two-tube  method  of  direct  transfusion  which  I  devised 
some  years  ago  is  especially  well  adapted,  the  usual 
methods  of  indirect  transfusion  being  imsuited  because 
of  the  likelihood  of  clot  formation  in  the  needles 
during  the  intervals.  The  citrate  method,  though, 
may  be  used  for  this  purpose,  and  possibly  may  prove 
to  be  the  method  of  election. 

Up  to  this  time  I  have  been  speaking  of  cases  of 
massive  bleeding  which  is  still  in  process,  but  there  is  a 
far  greater  class  which  must  be  considered  and  in 
which  the  keenest  judgment  is  required.  Many  cases 
arise  where  the  bleeding  has  been  quite  severe  and  the 
patient  comes  in  in  evident  distress  although  the 
source  of  the  hemorrhage  has  been  controlled.  Is  a 
transfusion  necessary,  or  is  it  not?  A  more  difficult 
question  could  hardly  be  propounded.  Where  there 
is  air-hunger,  I  proceed  at  once  to  transfusion ;  it  may 
be  that  supportive  treatment  would  save  the  day — in 


154  BLOOD  TRANSFUSION 

fact,  I  know  of  cases  where  it  did — but  the  margin 
of  safety  has  been  strained  to  the  uttermost  limits 
whenever  air-himger  is  in  evidence,  and  I  prefer  not 
to  trifle  with  it.  I  have  seen  several  fatalities  because 
of  the  delay  incidental  to  the  carrying  out  of  sup- 
portive measures.  However,  cases  of  air-hunger  are 
relatively  uncommon  and  really  offer  little  difficulty 
so  far  as  judgment  is  concerned. 

Volcanic  gastric  ulcers,  placenta  praevia,  typhoid 
bleeding  and  allied  conditions  at  times  offer  most 
difficult  problems  in  diagnosis,  prognosis  and  judg- 
ment. I  have  heard  the  statement  made  that  no  one 
ever  bleeds  to  death  from  a  gastric  ulcer  and  certain 
gynaecologists  maintain  that  a  fatal  ending  never  re- 
sults from  the  hemoiThage  of  a  ruptured  extra-uterine 
pregnancy,  both  of  which  statements  have  done  incalcu- 
lable harm.  There  is  no  form  of  bleeding  known  which 
cannot,  which  does  not,  at  times,  result  fatally,  how- 
ever insignificant  its  inception  may  have  been.  I  have 
personally  seen  several  deaths  from  bleeding  gastric 
ulcers,  from  ruptured  ectopic  pregnancies,  from  in- 
testinal hemorrhages  in  the  course  of  typhoid  fever 
and  from  a  number  of  other  hemorrhagic  conditions 
that  are  thought  to  be  non-fatal  by  many  men  who 
have  accepted  unfounded  assertions  without  investi- 
gation. I  will  admit  that  acute  hemorrhages  do  not 
culminate  fatally  in  the  vast  majority  of  instances, 


TRANSFUSION  FOR  ACUTE  CONDITIONS      155 

but  many  of  them  progress  so  near  to  a  fatal 
issue  that  any  prediction  as  to  the  ultimate  end  of 
an  actual  fulminating  bleeding  is  one  of  the  most 
foolhardy  things  I  know  of.  The  saving  mechanism, 
of  course,  in  these  affairs  is  the  automatic  fall  in 
blood-pressure  with  consequent  relief  of  tension  and 
slowing  of  the  blood  cm'rent,  which  favors  clot  forma- 
tion at  the  site  of  the  bleeding.  But  who  can  tell 
whether  the  vessel  at  fault  is  vein  or  artery,  large  or 
small  ?  And  what  is  to  be  the  deciding  point  in  choos- 
ing a  course  of  action — shall  we  allow  the  bleeding  to 
proceed  to  practical  exsanguination  with  great  risk  in- 
volved, or  shall  we  resort  to  supportive  measiu-es  and 
if  so — what,  and  when? 

Certain  measures  should  be  adopted  in  all  acute 
hemorrhages  because  certain  features  are  common  to 
all  of  them,  the  chief  points  of  difference  being  due, 
generally  speaking,  solely  to  the  anatomical  location 
of  the  affected  vessel  and  its  supporting  tissues.  An 
artery  is  an  artery  whether  it  is  in  the  stomach  or  the 
kidney,  and,  when  it  is  injm^ed,  bleeds  the  same  way 
in  either  place,  and  with  equal  harm.  But  the  tissues 
surrounding  the  stomach  artery  are  very  dissimilar 
from  those  surrounding  the  renal  vessel,  or  those  sm*- 
rounding  a  uterine  artery,  and  the  future  course  of 
a  hemorrhage  may  depend  a  great  deal  upon  these 
anatomical  differences. 


156  BLOOD  TRANSFUSION 

Therefore  rest,  sedatives,  an  ice-bag  over  the  bleed- 
ing area  if  accessible  or  convenient  (the  idea  being 
to  favor  contraction  of  the  blood  vessels),  elevation 
of  the  foot  of  the  bed  to  avoid  brain  anaemia,  plenty 
of  vs'ater  to  quench  the  thirst,  bandaging  the  ex- 
tremities, perhaps,  and  a  slow  infusion  of  a  moderate 
amount  of  salt  solution  to  maintain  a  semblance  of 
blood  bulk,  to  steady  a  faltering  blood-pressure  and  to 
relieve  thirst,  these  and  other  less  used  measures  are 
common  to  almost  any  form  of  hemorrhage.  Packing 
or  ligating  any  accessible  vessel  comes  in  the  same 
category,  after  which  general  remedies,  the  course  of 
treatment  is  differentiated. 

GASTRIC  ULCER 

In  a  subsiding  gastric  hemorrhage  it  is  wise  to 
restrict  the  liquids  in  order  to  keep  the  blood  bulk  as 
low  as  possible,  but,  if  the  case  has  proceeded  almost 
to  exsanguination,  it  is  advisable  to  give  slow  salt, 
or  sugar  solution  per  rectum,  or  a  slow  infusion  of  not 
over  500  to  1000  c.c.  One  must  always  be  on  guard, 
though,  in  concluding  that  any  gastric  bleeding  has 
subsided  or  is  subsiding.  The  weaker  a  patient  gets 
and  the  lower  his  blood  pressure,  the  slower  is  the  bleed- 
ing and  the  longer  does  it  take  the  stomach  to  fill  up ; 
the  warning  nausea,  too,  is  less  pronounced  and  vomit- 
ing of  contained  blood  may  not  take  place  until  the 
stomach  becomes  full  to  overflowing. 


TRANSFUSION  FOR  ACUTE  CONDITIONS      157 

It  would  take  me  too  far  afield  to  discuss  the  pros 
and  cons  of  gastro-enterostomy  or  pyloroplasty  or 
simple  resection  or  scarification  of  an  ulcer  for  bleed- 
ing. Ligation  of  a  bleeding  point  is  absolutely  the 
surest  way  of  stopping  hemorrhage,  but  there  are 
times  when  it  is  neither  the  safest,  surest  nor  wisest 
thing  to  do.  I  have  seen  cases  of  gastric  bleeding 
where  prompt  exploration  and  gastro-enterostomy 
gave  brilliant  results,  and  I  have  seen  cases  where  a 
saner  judgment  might  have  decided  against  the  opera- 
tion which  ended  fatally.  For  the  purpose  of  this 
discussion,  I  can  only  say  that  with  a  patient  in  ex- 
tremis from  bleeding,  transfusion  before,  during  or 
immediately  after  operation  considerably  enhances  the 
chances  of  success.  The  first  patient  I  ever  trans- 
fused was  of  this  type  and  several  subsequent  cases 
have  done  equally  well.  Even  when  the  patient  is 
not  exsanguinated,  it  is  wise  to  have  a  suitable  donor 
on  hand  in  case  of  emergency. 

Finally  there  is  a  group  of  gastric  cases  in  which 
for  one  reason  or  another  operation  is  out  of  the  ques- 
tion. In  these  and  in  all  other  forms  of  apparently 
intractable  bleeding  where  all  the  usual  measures  to 
stop  it  have  been  unavailing,  I  make  it  a  fixed  rule  to 
do  a  blood  transfusion  if  the  blood-pressure  reaches 
70  mm.  of  mercury,  and  not  infrequently  I  transfuse 


158  BLOOD  TRANSFUSION 

with  the  pressure  around  100  mm.  The  rate  of  inflow 
in  these  oases  must  be  carefully  guarded,  and  the 
amount  of  blood  given  rather  small,  for  fear  of  raising 
the  pressure  too  suddenly  and  too  high,  thus  exciting 
renewed  bleeding.  In  the  last  case  500  c.c.  improved 
the  patient's  condition  markedly  and  a  prompt  cessa- 
tion of  the  bleeding  took  place,  but  I  tliink  350  or  400 
c.c.  is  a  safer  quantity  to  give.  It  is  too  much,  per- 
haps, to  expect  a  large  artery  to  cease  pouring  out 
blood  by  a  simple  transfusion,  but  one  rarely  has  a 
chance  to  do  a  transfusion  where  a  really  big  vessel  is 
open,  and  where  the  smaller  ones  are  at  fault  a  slowing 
of  the  current  has  already  taken  place  before  the  trans- 
fusion is  started.  In  all  those  cases  that  I  have  done, 
except  the  actually  moribund,  the  bleeding  has  stopped 
with  the  accession  of  new  blood.  In  one  it  started  up 
again  one  month  later  but  stopped  permanently  with  a 
second  transfusion.  Just  why  it  should  stop  is  prob- 
lematical, but  we  know  fresh  human  blood  exerts  a 
beneficial  effect  on  coagulation  in  any  and  all  forms  of 
bleeding.  Hence  experience  has  shown  that  when  all 
other  means  fail,  blood  transfusion,  properly  managed, 
should  be  tried.  Even  in  those  cases  where  the  bleeding 
has  ceased,  it  is  at  times  advisable  to  transfuse  because 
of  the  profound  prostration,  and  at  a  later  stage  one 
or  more  transfusions  may  be  indicated  to  relieve  the 
severe  ansemia  and  to  give  a  fresh  start  in  the  upbuild- 


TRANSFUSION  FOR  ACUTE  CONDITIONS       159 

ing  process.  Especially  is  this  so  in  those  cases  of 
repeated  hemoiThages  where  the  blood  forming  organs 
have  been  called  upon  so  often  that  they  finally  fail 
to  respond.  A  case  in  point  is  that  of  a  nurse  who 
became  chronically  anaemic  and  prostrated  from  sev- 
eral gastric  bleedings.  Rest  in  bed,  forced  feeding 
and  drug  therapy  utterly  failed,  but  two  transfusions 
gave  her  a  new  lease  on  life  and  her  hemorrhages  have 
not  recurred.  She  is  now  in  perfect  health  and  actively 
engaged  in  her  profession. 

INTESTIX^VL  BLEEDING 

The  intestinal  hemorrhages  differ  little  from  the 
gastric  ones.  Usually  encountered  during  the  course 
of  typhoid  fever,  most  of  them  cease  spontaneously 
when  the  pressure  falls,  but  they  tend  to  recur  when 
it  rises.  Some  of  them,  though,  do  not  cease  and  the 
old  question  of  procedure  arises.  It  is  so  difficult  to 
distinguish  between  benign  and  dangerous  intesti- 
nal hemorrhages.  With  the  advent  of  sodium  citrate 
transfusion,  and  its  more  thorough  comprehension,  it 
seems  likely  that  transfusion  will  be  considered  as 
indicated  in  more  cases  of  typhoid  bleeding  than  is  at 
present  the  custom,  especially  if  an  immune  donor 
can  be  found.  The  disease  itself  is  bad  enough  and 
it  has  been  a  mystery  to  me  how  any  of  these  cases 
recover  after  the  debilitating  influence  of  the  terrific 
hemorrhages  so  frequently  seen.     At  present  it  is 


160  BLOOD  TRANSFUSION 

rather  uncommon  to  transfuse  these  cases,  because  of 
the  necessity  for  disturbing  them  and  the  consequent 
danger  of  making  matters  worse.  I  have  done  but 
one  case  and  that  one  had  perforated  in  addition  to 
having  had  several  hemorrhages.  In  spite  of  his  mori- 
bund condition,  he  withstood  operation  fairly  well 
and  lived  four  days,  but  was  too  weak  to  survive. 

POST-OPERATIVE  BLEEDING 

I  have  considered  the  differential  diagnosis  of 
post-operative  hemorrhages  rather  in  detail  in  Chap- 
ter II.  In  the  present  connection,  it  is,  therefore, 
sufficient  to  say  that  where  a  correct  diagnosis  of  the 
trouble  has  been  promptly  made,  it  usually  suffices 
to  open  the  wound,  find  the  bleeding  point  and  tie  it. 
The  patients  are  always  badly  shocked,  but  generally 
respond  to  rest,  warmth  and  salt  infusions.  A  case 
in  point  occurred  in  November,  1916.  A  woman  had 
undergone  an  extensive  pelvic  operation  and  was  re- 
turned to  her  room  in  good  condition.  Suddenly, 
four  or  five  hours  later,  her  nurse  was  astonished  to 
find  her  pulse  very  rapid  and  irregular,  her  face 
blanched  and  respirations  rapid  and  shallow.  The 
cause  was  evident  in  the  blood  that  was  pouring  out 
of  the  vagina  along  a  drain.  Prompt  reopening  of 
the  abdominal  incision  revealed  considerable  blood  in 
the  lower  abdomen,  the  source  of  which  was  the  uter- 


TRANSFUSION  FOR  ACUTE  CONDITIONS      161 

ine  stump.  A  few  sutures  stopped  the  bleeding  and 
the  patient  was  returned  to  her  bed  to  undergo  a 
somewhat  delayed  but  satisfactory  convalescence. 
Her  condition  improved  the  moment  the  leakage  was 
stopped  and  a  salt  solution  infusion  did  the  rest. 

Time  ought  never  be  wasted  in  attempting  to  stop 
a  post-operative  hemorrhage  by  means  other  than  re- 
opening of  the  wound  and  catching  the  bleeding  point. 
Extraneous  blood  in  the  peritoneal  cavity  can  do  no 
possible  good  and  the  formation  of  an  heematoma  in 
any  wound  only  encourages  infection.  Where  the 
bleeding  has  escaped  detection  or  has  been  so  exces- 
sive as  to  preclude  reopening  of  the  incision,  I  have 
urged  and  repeatedly  carried  out  transfusion,  during 
the  course  of  which  the  secondary  operation  has  been 
successfully  done.  The  method  of  procedure  is  to 
take  the  patient  to  the  operating  room  and  start  the 
transfusion,  either  direct  or  indirect  but  preferably 
the  former,  under  local  ansesthesia.  With  the  intro- 
duction of  comparatively  little  (hardly  over  150  c.c.) 
of  fresh  blood  the  patient  invariably  takes  on  renewed 
life  and  the  blood-pressiu'e  rises.  The  moment  this 
stage  is  reached  ether  is  started — always  ether  because 
of  its  stimulating  effect  on  the  heart  action — and  with 
light  but  full  anaesthesia  the  woimd  is  opened.  Dur- 
ing the  course  of  the  manipulations  necessary  to  find, 

secure,  and  tie  the  offending  vessel  or  vessels  the 
n 


162  BLOOD  TRANSFUSION 

transfusion  is  interrupted,  since  to  continue  amounts 
to  but  little  more  than  wasteful  pumping  in  and 
pumping  out  at  the  same  time.  But  the  moment  the 
bleeding  point  is  secure,  the  blood  flow  is  again  started 
and  carried  to  its  conclusion.  Some  of  the  most  bril- 
liant results  imaginable  have  been  secured  in  this  type 
of  case.  One  of  these  was  that  of  a  woman  who  sud- 
denly collapsed  a  few  hours  after  an  extensive  ab- 
dominal operation  during  the  com*se  of  which  the 
appendix  and  gall-bladder  had  been  removed.  Dur- 
ing the  course  of  a  transfusion  the  abdomen  was  re- 
opened and  found  to  be  filled  with  blood  which  was 
coming  from  the  cystic  artery  which  had  slipped  its 
ligature.  It  was  secured,  the  patient  was  given  a 
little  extra  blood  to  make  up  the  loss  and  a  satis- 
factory convalescence  ensued.  Another  was  a  kidney 
case  where,  after  a  nephrotomy  for  stone,  sudden 
bleeding  took  place  of  such  severity  that  the  wound 
had  to  be  reopened  and  resutured,  an  undertaking 
that  would  have  been  impossible  in  this  instance  with- 
out coincident  transfusion.  Still  another  was  bleed- 
ing after  a  gastro-enterostomy.  These  and  others  go 
to  form  a  most  satisfactory  series. 

RUPTURED  ECTOPIC  PREGNANCY 

Ruptured  extra-uterine  pregnancy,  of  which  I 
have  spoken  more  in  detail  elsewhere,  should  be 
handled  exactly  like  a  post-operative  hemorrhage. 


TRANSFUSION  FOR  ACUTE  CONDITIONS      163 

Where  the  patient's  condition  warrants,  which  is  in 
the  majority  of  cases,  prompt  operation  should  be 
done.  Where  there  is  some  doubt  concerning  the 
abihty  to  stand  interference,  rest,  sedatives  and  a 
slow  infusion  of  moderate  amounts  of  salt  solution  will 
occasionally  bring  back  a  woman  sufficiently  to  with- 
stand operation.  In  order  to  do  this  the  greatest  care 
and  judgment  must  be  exercised  and  the  operation 
should  be  done  as  soon  as  the  patient  strikes  the  up- 
grade, because  it  occasionallyhappens  that  the  improve- 
ment is  fleeting  and  unless  the  opportunity  is  grasped 
the  moment  it  presents,  the  chance  is  lost,  for  a  second 
opportunity  comes  but  rarely.  Those  cases  which 
fail  to  respond  or  which  are  so  profoundly  shocked 
as  to  preclude  supportive  measures  should  be  imme- 
diately transfused,  and  operated  on,  as  outlined  under 
post-operative  hemorrhage.  A  case  of  this  type  oc- 
curred in  my  practice  not  many  months  ago.  A 
young  married  woman,  patient  of  Dr.  E.  H.  Richard- 
son, suddenly  had  an  excruciating  pain  in  her  lower 
abdomen  while  at  stool.  She  fainted  and  a  Httle  later 
her  physician  diagnosed  ruptured  extra-uterine  preg- 
nancy and  sent  her  to  the  hospital  where  an  attempt 
was  made  to  relieve  her  from  a  dangerous  state  of 
prostration.  After  two  or  three  hours  a  shght  im- 
provement came  to  pass,  but  it  was  extremely  fleet- 


164  BLOOD  TRANSFUSION 

ing,  and  she  shortly  afterward  became  definitely 
worse.  Transfusion  and  coincident  operation  were 
followed  by  a  perfectly  normal  convalescence. 

POSTPARTUM    BLEEDING 

It  has  been  my  fortune  to  be  called  upon  in  a  num- 
ber of  postpartum  hemorrhages  and  as  a  result  of 
the  experience  thus  gained,  whenever  an  obstetrician 
calls  for  help,  I  always  know  that  there  is  no  doubt 
of  there  having  been  a  real  hemon-hage,  for  of  all 
medical  men,  obstetricians  are  the  most  complacent  in 
the  face  of  conditions  that  are,  to  say  the  least,  trying. 
This  attitude  is  doubtless  essential  to  the  make-up  of 
a  successful  obstetrician,  since  it  would  obviously  be 
rather  harrowing  for  him  to  be  upset  at  the  sight  of 
considerable  amounts  of  blood — a  bloodless  delivery 
is  unknown — but  I  sometimes  feel  that  a  certain  de- 
gree of  sensitiveness  would  be  to  his  advantage.  Every 
case  I  have  seen  has  been  practically  exsanguinated, 
several  being  absolutely  beyond  hope  by  the  time  I 
arrived. 

But  the  obstetricians  are  not  only  complacent  in 
the  face  of  danger,  they  are  the  most  optimistic  set 
of  men  imaginable.  They  are  so  accustomed  to  wit- 
nessing a  prompt  return  to  well-being  after  profuse 
bleedings  that  the  slightest  improvement  gives  them 
inordinate  satisfaction  and  comfort,  so  much  so  that 


TRANSFUSION  FOR  ACUTE  CONDITIONS      165 

they  are  prone  to  delay  matters  until  their  patient  is 
actually  in  extremis.  I  have  lost  two  or  three  patients 
by  taking  stock  in  their  superior  knowledge  of  post- 
partum hemorrhages,  when  my  own  judgment  urged 
a  most  hurried  transfusion,  so  that  now  I  proceed 
along  the  theory  that  if  an  obstetrician  really  con- 
siders a  transfusion  he  must  have  been  at  least  a  bit 
frightened,  and  if  the  bleeding  was  sufficient  to 
frighten  him,  it  must  have  been  a  terrific  hemorrhage. 
And  since  adopting  this  course,  my  results  in  obstet- 
rical bleedings  have  been  better.  I  transfuse  without 
delay  nearly  every  one  I  see.  In  two  instances, 
though,  bandaging  the  extremities,  salt  infusions, 
uterine  massage,  packing,  rest  and  morphine  sufficed. 
From  all  I  can  gather  the  chief  cause  of  post- 
partum hemorrhage  seems  to  be  atony  of  the  uterus 
resulting  from  prolonged  labor,  dystocia,  and  high 
forceps.  Whether  these  are  actual  causes  or  merely 
incidental,  I  am  not  prepared  to  say.  Another  factor, 
possibly  it  is  the  primary  one,  is  the  failure  of  ergot 
or  pituitrin  to  bring  about  uteiine  contractions.  I 
frequently  find  that  during  the  labor  it  has  been  neces- 
sary to  mechanically  dilate  the  cervix,  always  a  pro- 
cedm*e  that  causes  great  shock.  The  storj^  is,  that 
with  the  oncoming  of  intractable  bleeding  the  uterus 
was  packed ;  this  stopped  the  bleeding  to  a  certain  ex- 
tent, but  it  seemed  to  add  still  further  to  the  shock. 


166  BLOOD  TRANSFUSION 

either  by  stretching  an  organ  that  was  trpng,  or 
should  have  been  trying,  to  contract  or  still  further 
dilating  the  cervix  or  keeping  it  dilated  when  it  ought 
to  have  been  getting  smaller,  a  question  for  the  obstet- 
rician to  decide. 

In  one  striking  case,  the  consulting  obstetrician, 
Dr.  J.  M.  H.  Rowland,  felt  that  the  bleeding  was 
coming  entirely  from  a  deeply  torn  cerv^ix,  but  the 
patient  was  in  such  a  precarious  state  that  he  dared 
not  touch  her.  During  the  course  of  a  transfusion, 
though,  he  removed  the  packs,  verified  his  diagnosis 
and  repaired  the  damage.  The  patient  improved  won- 
derfully as  soon  as  the  packs  were  removed;  there- 
fore since  the  bleeding  soui'ce  had  been  controlled, 
they  were  not  replaced.  A  normal  convalescence 
ensued.  In  another  case,  that  of  Dr.  Carl  Wilson, 
the  patient  was  markedly  improved  by  transfusion, 
but  she  had  lost  so  much  blood  that  it  was  deemed 
unwise  to  touch  the  packs  at  that  time.  Half  of  them 
were  removed  on  the  following  day  and  the  remainder 
on  the  third  day  without  further  bleeding,  the  patient 
making  a  good  recover}\ 

PLACENTA    PREVIA    BLEEDING 

Of  all  the  obstetrical  hemorrhages,  the  placenta 
prffivias  are  the  saddest,  because  the  child  is  frequently 
lost  and  the  mother  either  has  a  narrow  escape  or  is 
lost  too.    It  has  been  my  good  fortune  to  have  saved 


TRANSFUSION  FOR  ACUTE  CONDITIONS      167 

a  few  mothers  by  prompt  transfusion — but  I  must 
chronicle  one  death,  that  of  a  primipara  who,  after 
bleeding  for  two  weeks  off  and  on,  was  withheld  from 
delivery  by  an  experienced  obstetrician  in  order  to 
give  the  child  a  better  chance  for  life.  One  morning 
the  hemoiThage  became  quite  profuse  and  a  hurried 
delivery  by  version  was  done,  as  a  result  of  which  the 
child  died,  but  the  mother  seemed  to  be  all  right.  Five 
hours  later  an  apparent  atony  of  the  uterus  ensued 
which  was  heralded  by  a  terrific  gush  of  blood.  When 
I  arrived  the  most  harrowing  air-hunger  was  in  evi- 
dence and  I  attempted  a  rapid  transfusion,  but  it  was 
only  another  one  of  those  cases  which  must  go  on  the 
records  with  the  comment  of  "  too  late  "  opposite  the 
name.^ 

In  one  instance  where  the  bleeding  had  been  in 
progress  for  some  hom-s  and  the  patient  seemed  to 
be  in  very  bad  condition,  I  started  a  direct  transfusion 
and  revived  her  to  such  extent  that  it  was  safe  to 
etherize  her,  whereupon,  the  blood  still  pouring  into 

^  This  type  of  blood  loss  might  well  be  termed  "  Cumula- 
tive Bleeding "  since  it  is  the  repeated  small  blood  losses 
spread  out  over  a  considerable  period  that  place  the  patient 
in  such  weakened  condition,  frequently  unsuspected,  that  a 
final  sudden  sharp  hemorrhage  proves  disastrous.  Ordinarily 
this  last  hemorrhage  would  not  be  considered  really  alarming 
were  it  not  for  the  "  Cumulative  effect  "  of  the  previous 
bleedings. 


168  BLCX)D  TRANSFUSION 

her  veins,  the  obstetrician  did  a  hurried  version  and 
extraction,  and  one  hfe  at  least  (the  mother's)  was 
saved.  In  another  case  transfusion  immediately  after 
delivery  made  up  the  blood  loss,  and  both  mother  and 
babe  were  saved. 

There  can,  of  course,  be  no  absolute  routine  for 
these  cases  because  many  of  them  are  delivered  by 
the  ideal  Cesarean  section  and  run  little  danger  so 
far  as  bleeding  is  concerned.  But  it  does  seem  rea- 
sonable to  suggest  preliminary  preparations  for  trans- 
fusion in  those  instances  where  C^esarean  section  is 
not  to  be  done  and  where  bleeding  has  been  going 
on  for  some  time,  and  where  the  patient  is  in  bad 
condition.  The  maternal  mortality  will  thus  surely 
be  reduced.  Preliminary  blood  tests  and  preparations 
for  transfusion  would  be  especially  helpful  in  those 
instances  of  known  placenta  praevia  where  attempts 
are  being  made  to  carry  the  mother  along  in  order 
to  get  a  viable  child. 

PREMATURE  SEPARATION  OF  THE  PLACENTA 

I  have  done  a  transfusion  in  still  another  form  of 
obstetrical  bleeding,  though  a  most  rare  one.  It  was 
an  instance  of  premature  separation  of  the  placenta 
in  a  woman  eight  months  pregnant  and  previously 
well.  At  operation  by  Dr.  J.  Whitridge  Williams  a 
tremendous  quantity  of  blood  was  found  in  the  uterus, 


TRANSFUSION  FOR  ACUTE  CONDITIONS      169 

which,  after  being  emptied  of  its  dead  incubus,  utterly 
failed  to  contract  and  had  to  be  removed.  The  patient 
was  terribly  exsanguinated,  but  with  careful  handling 
seemed  about  to  come  back,  when,  seventy-two  hours 
after  operation,  she  took  a  turn  for  the  worse,  and 
seemed  in  such  imminent  danger  that  a  transfusion 
was  done.  Her  recovery  after  that  was  slow  but 
uneventful.^ 

From  the  foregoing  surv^ey,  it  will  be  apparent 
that  blood  transfusion  may  be  of  service  in  a  number 
of  different  varieties  of  acute  blood  loss  if  judiciously 
employed.  The  most  difficult  feature  in  connection 
with  it  seems  to  be  not  where  it  should  be  used,  but 
when,  and  it  may,  perhaps,  be  in  order  to  suggest 
that  the  best  results  will  be  obtained  in  those  cases 
where  the  patient  has  not  been  allowed  to  proceed  too 
far  in  the  bleeding  course.  Xo  one  realizes  better 
than  I  the  difficulties  encountered  in  deciding  just 
when  the  actual  limit  of  bleeding  has  been  reached, 
and  for  that  reason  it  seems  that  one  ought  never 
wait  for  the  actual  limit  of  endm'ance.  Onlj'  too 
often  a  bleeding  patient  will  actually  be,  or  seem  to 
be,  in  good  shape  almost  to  the  very  end,  thus  render- 
ing accurate  judgment  all  but  impossible.    A  stable 

^  Since  writing  this  I  have  liad  another  similar  case,  that 
of  Drs.  Dobbin  and  Bergland.  Transfusion  and  Caesarean 
section  saved  the  mother. 


170  BLOOD  TRANSFUSION 

blood-pressure  that  is  well  within  the  limits  of  safety 
will  sometimes  take  a  tumble  from  which  it  never 
recovers.  Acute  hemorrhage  from  any  cause  is  a 
dangerous  thing;  it  ought  never  be  trifled  with;  at 
times  it  ends  with  great  unexpectedness,  once  and 
for  all. 

REFERENCES 

Bernheim,  B.  M. :  "  The  Limits  of  Bleeding  Considered  from 
the  Clinical  Standpoint."  Amer.  Jour,  of  the  Medical 
Sciences^  April,  1917. 

Crile,  G.  W. :  "  Hemorrhage  and  Transfusion."  Appleton, 
1909. 

Crile,  G.  W. :  "  Anaemia  and  Resuscitation."    Appleton,  1914. 

David,  V.  C,  and  Curtis,  Arthur  H.:  "  Experiments  in  the 
Treatment  of  Acute  Anaemia  by  Blood  Transfusion  and 
by  Intravenous  Saline  Infusion."  Surg.,  Gynecology  and 
Obgtet.,  October,  1912. 

Levinson,  Louis  A. :  "  Leukocytosis  a  Deceptive  Sign  in  Ab- 
dominal Hemorrhages."  J.  A.  M.  A.,  April  17,  1915. 

Mayo,  Wm.  J. :  "  Hemorrhage  from  the  Stomach  and  Duo- 
denum." Surgery,  Gynecology  and  Obstetrics,  May, 
1908,  pp.  451-454. 

Peterson,  Edward  W. :  "  Results  from  Blood  Transfusion  in 
the  Treatment  of  Severe  Post-operative  Anaemia  and 
the  Hemorrhagic  Diseases,"  J.  A.  M.  A.,  April  22, 
1916,  vol.  Ixvi. 

Richardson,  E.  H. :  "Treatment  of  the  Emergency  Cases  of 
Ectopic  Pregnancy."  Bulletin  of  the  Johns  Hopkins 
Hospital,  September,  1916,  vol.  xxvi. 

Thompson,  J.  E. :  "  Remarks  on  Fatal  Hemorrhage  from 
Erosion  of  the  Gastroduodenal  Artery  by  Duodenal  Ul- 
cers."  Anrmls  of  Surgery,  May,  1913. 


CHAPTER  IX 

TRANSFUSION  FOR  ANEMIC  AND  DEBILITATED 
CONDITIONS  IN  GENERAL.    BLOOD  DOSAGE 

Unexploited  as  the  purely  secondaiy  amemias 
now  are,  I  venture  to  predict  that  they  will  eventually 
play  a  conspicuous  part  in  developing  blood  transfu- 
sion therapy  to  its  fullest  usefulness.  Up  to  the  pres- 
ent only  those  conditions  have  been  subjected  to  trans- 
fusion that  have  demanded  it  as  a  common  sense  pro- 
cedure or  were  of  such  character  that  nothing  of  a 
known  nature  could  help  and  something  in  the  nature 
of  the  unknown  was  deemed  permissible  as  a  trial. 
Many  reasons  suggest  themselves  as  the  cause  of 
this,  chief  among  which  was  the  previous  technical 
difficulty  of  carrying  out  a  transfusion,  a  state  of 
affairs  that  has  now  happily  been  overcome. 

In  June,  1913,  I  read  a  paper  before  the  Ameri- 
can Medical  Association,  then  meeting  in  Minneapo- 
lis, entitled,  "  Therapeutic  Possibilities  of  Transfu- 
sion," during  the  course  of  which  I  asked  these  ques- 
tions :  "Is  transfusion  purely  and  simply  an  emer- 
gency operation?  May  not  its  chief  field  of  useful- 
ness be  rather  as  a  therapeutic  agent,  and  have  we 
not  almost  entirely  overlooked  this  possibility?  "  Cer- 

171 


17«  BLOOD  TRANSFUSION 

tain  predictions  were  then  made,  notably  the  fui-ther 
and  continued  use  of  transfusion  in  pernicious  anae- 
mia, and  it  was  suggested  that  many  secondary  anae- 
mias might  be  tremendously  helped  by  the  addition 
of  fresh  blood,  especially  in  the  case  of  those  whose 
path  back  to  health  was  so  slow  and  circuitous.  I 
argued  that  transfusion  would  give  an  irrepressible 
impetus  to  many  individuals  whose  debilitated,  anae- 
mic body  had  all  but  ceased  to  respond  to  the  usual 
treatment  of  rest,  fresh  air,  diet  and  the  variously 
used  drugs. 

Subsequent  events  have  proved  my  contention,  as 
is  evidenced  by  the  continually  expanding  field  of 
blood  transfusion  therapy,  but  certain  features  con- 
nected with  it  are  still  um*ecognized  and  much  more 
remains  to  be  done,  chiefly  the  education  of  physicians 
to  a  realization  that  chronic  secondary  anaemia  is  a 
distressing,  serious  condition  which  demands  for  its 
relief  more  than  renewed,  interchangeable  prescrip- 
tions and  a  little  rest.  Our  present  day  therapy  differs 
but  slightly  from  that  in  vogue  years  and  years  ago — 
rest,  forced  feeding,  iron,  arsenic,  etc. — in  fact  about 
the  only  real  change  is  in  the  arsenical  preparation 
now  used;  the  cacodylates  have  supplanted  Fowler's 
solution  in  the  affections  of  most  physicians.  The 
thought  seems  never  to  occur  that  anaemia  means 
blood  loss,  blood  depletion,  and  that  the  best  way  of 


TRANSFUSION  FOR  ANEMIA  173 

supplying  the  deficiency  is  to  actually  put  new  blood 
into  the  unfilled  veins. 

If  a  woman  suffers  repeated  hemorrhages  from 
uterine  fibroids,  she  is  put  to  bed  for  two  or  three 
weeks  in  order  to  get  into  condition  for  an  operation, 
and  if  she  refuses  to  be  operated  on  she  is  put  to  bed 
and  treated  in  the  same  way  anyhow.  Or  if  her  medi- 
cal attendants  are  a  bit  careless,  she  may  be  operated 
on  without  the  building-up  process — so  many  women 
hare  come  through  pelvic  operations  in  spite  of  pro- 
found anaemia  that  it  is  rather  common  to  disregard  it 
as  a  real  menace.  Convalescence  might  be  rather 
stormy  in  some  and  rather  prolonged,  but  they  get 
well,  so  why  bother? 

In  certain  of  the  intestinal  bleedings,  many  of 
obscure  origin  and  perhaps  not  amenable  to  surgical 
intervention,  how  the  poor  patients  are  put  through 
rest  cm-e  processes,  not  once  but  repeatedly,  until 
there  finally  comes  a  time  when  the  poor  blood-form- 
ing organs  simply  refuse  to  build,  in  spite  of  pharma- 
ceutical lashings  prolonged  and  various — pale,  thin, 
weak  individuals,  unable  to  sleep,  unable  to  eat,  fear- 
ful of  another  hemorrhage  perhaps,  desirous  of  per- 
forming their  wonted  tasks  but  physically  unfit, 
always  tired  and  discom'aged,  a  bm'den  to  themselves 
and  their  relatives  and  friends.  Certainly  they  cannot 
eat,  and  what  little  food  does  pass  their  lips  is  tasteless. 


174  BLOOD  TRANSFUSION 

The  colorless  tongue  denotes  tasteless  food  and  an 
ansemic  state.  It  is  always  so  in  anaemia,  and  the 
appetite  changes  only  when  the  blood  pictui*e  changes. 

There  are  many  other  individuals,  notably  those 
cases  of  chronic  illness,  who  finally  come  to  operation 
or  exploration,  not  because  they  have  been  diagnosed, 
but  because  they  have  remained  ill,  all  efforts  to  the 
contrary  notwithstanding,  and  a  delayed  surgical  in- 
vestigation suggests  itself  as  the  only  remaining  avenue 
of  hope.  These  are  very  bad  surgical  risks,  for  whom  a 
transfusion,  prior  to  or  during  operation,  would  en- 
hance the  chances  of  recovery  and  provide  a  shortened, 
tranquil  convalescence  in  place  of  the  precarious  one 
almost  surely  to  be  encountered  without  the  addition 
of  new  blood.  In  a  paper  entitled  "  Blood  Trans- 
fusion, Indications  and  Results,  Based  on  Observa- 
tions of  212  Transfusions,"  Libman  and  Ottenberg 
call  attention  to  this  class  of  cases,  saying,  "Among 
the  most  satisfactory  transfusions  in  the  whole  series 
were  some  of  those  done  preliminary  to  operation  in 
patients  whose  desperate  condition  would  otherwise 
have  contra-indicated  any  other  operation.  There 
were  23  pre-operative  transfusions  and  in  13  of  them 
the  result  was  decisive  and  the  patient  recovered." 

There  is  another  group,  for  whom  post-operative 
transfusion  would  be  an  invaluable  aid — cases  whose 
convalescence  is  stormy  and  delayed  although  the  con- 


TRANSFUSION  FOR  ANJEMIA  175 

dition  at  operation  may  have  been  quite  satisfactory. 
The  shock  has  been  too  great,  an  accident  has  hap- 
pened or  a  post-operative  prostration  quite  unwar- 
ranted by  the  condition  prior  to  operation  has  ensued. 
Instead  of  two  or  three  weeks  in  the  hospital,  the  visit 
lengthens  to  five  or  six  weeks  for  these  cases,  and  the 
building  up  process  may  even  have  to  be  continued  at 
home.  Those  who  apparently  cannot  come  back  after 
operation  under  ordinary  treatment  can  do  so  in  many 
instances  if  given  a  little  blood.  Peterson  reports 
such  a  case,  the  patient  being  a  little  boy  who  had 
had  a  pneumonia  during  whose  course  an  empyema, 
for  which  he  came  to  operation,  developed.  He  ran 
a  very  high  temperature,  gradually  lost  weight  and 
strength,  refused  all  nourishment  and,  to  make  mat- 
ters worse,  developed  a  diarrhoea.  No  pocketing  of 
the  empyema  cavity  could  be  discovered,  and  the  case 
was  considered  hopeless,  when  as  a  last  resort  it  was 
decided  to  try  blood  transfusion.  With  the  mother 
acting  as  donor,  235  c.c.  of  blood  was  transfused,  and 
from  that  moment  the  child  began  to  improve.  His 
temperature  dropped  immediately,  remained  down, 
and  an  uninterrupted  recovery  ensued.  Could  any- 
thing be  more  illuminating? 

Another  instructive  case,  one  of  my  own,  is  that  of 
a  man  who  had  had  a  gastric  resection  for  carcinoma. 
In  bad  condition  prior  to  operation  and  quite  aneemic, 
his  post-operative  course  was  steadily  downward.  His 


176  BLOOD  TRANSFUSION 

wouiid  broke  down,  he  was  unable  to  take  or  retain 
nourishment,  and  he  began  to  run  a  temperature  very 
suggestive  of  a  deep-seated  infection.  His  red  cells 
numbered  1,900,000,  while  his  haemoglobin  was  21 
per  cent.  He  was  pale,  desperately  weak,  absolutely 
without  hope,  and  he  had  the  anxious  expression,  the 
cold  clammy  skin  so  characteristic  of  those  in  utter 
prostration.  I  gave  him  500  c.c.  of  citrated  blood, 
and  three  days  later  he  had  a  red  count  of  3,260,000 
cells  and  a  haemoglobin  of  31  per  cent.,  while  his  tem- 
perature had  changed  its  type,  and  was  running  a 
rather  irregular  course  around  the  normal  base  line. 
His  wound,  too,  began  to  take  on  renewed  vigor,  and 
the  man  himself  began  to  look  about.  But  the  work 
was  not  finished.  In  order  to  clinch  matter,  I  gave 
him  another  smaller  dose  of  blood  eight  days  after 
the  first,  and  from  that  moment  on,  his  convalescence 
was  rapid  and  uninterrupted. 

Other  examples  abound,  but  these  foregoing  are 
sufficient  to  indicate  the  necessity  for  an  awakening 
on  the  part  of  physicians  and  surgeons  to  certain 
definite  deficiencies  in  their  handling  of  anaemic  de- 
bilitated states.  They  have  failed  to  recognize  the 
benefits  held  out  in  the  form  of  blood  transfusion.  If 
a  person  suffers  a  sudden  loss  of  great  volumes  of 
blood,  we  make  up  the  deficiency  by  adding  fresh 
blood.    Why,  then,  do  we  not  do  likewise  in  the  many 


TRANSFUSION  FOR  ANEMIA  177 

secondary  anaemias  that  also  suffer  blood  losses  but 
in  smaller  amounts  and  over  longer  periods?  Why 
persist  in  keeping  these  people  incapacitated  when 
a  transfusion  will  help  them  so  tremendously?  How 
can  an  ulcer  heal  when  there  is  not  blood  enough  to 
allow  its  base  to  become  healthy  ?  How  can  a  patient 
eat  when  everything  is  tasteless  and  the  very  sight 
of  food  produces  nausea?  Of  what  use  is  the  food 
when  it  reaches  the  stomach,  if  there  is  not  blood 
enough  to  take  it  up,  if  it  simply  putrefies  and  turns  to 
gas  and  causes  the  distressing  distention  of  anaemia? 
I  have  transfused  a  few  of  the  chronics,  and  the  new 
blood  has  done  more  to  restore  hope  and  sleep  and 
appetite  than  weeks  of  rest  and  barrels  of  iron  and 
arsenic.  I  do  not  decry  these  necessan^  adjuvants 
in  the  least;  on  the  contrary,  I  advise  their  constant 
use  and  have  seen  splendid  results  obtained.  I  merely 
deprecate  and  condemn  their  promiscuous  employ- 
ment in  conditions  beyond  their  therapeutic  reach. 
They  can  do  a  certain  amount,  but  in  many  cases  they 
are  absolutely  worthless,  and  in  many  of  these  one  or 
more  transfusions  will  almost  produce  a  miracle,  after 
which  the  drug  and  rest  therapy  maj^  be  judiciously 
resumed.  This  has  been  proved  but  it  has  not  been 
recognized. 

Thus  it  will  probably  come  to  pass  that  the  aid  of 
blood  transfusion  will  be  invoked  as  the  usual  thing 

12 


178  BLOOD  TRANSFUSION 

in  many  conditions  where  its  use  at  the  present  time 
is  decidedly  a  rarity,  and  almost  of  the  experimental 
variety.  This  will  be  a  definite  advance  in  many  ways, 
particularly  as  regards  our  knowledge  of  blood  dosage, 
a  matter  that  hitherto  has  been  almost  totally  neglected 
for  reasons  quite  obvious.  As  matters  stand  now,  we 
give  from  five  to  ten,  or  even  twelve  hundred  cubic 
centimetres  of  blood  in  cases  of  actual  voluminous 
blood  loss,  the  exact  amount  depending  almost  entirely 
upon  the  ability  of  the  donor  to  stand  the  depletion. 
Lesser  amounts  are  transfused  where  the  blood  loss 
has  not  been  so  great,  and  to  a  certain  extent,  in  those 
conditions  of  impaired  coagulation  apparatus.  The 
conviction  is  prevalent  that  comparatively  small  doses 
of  blood  are  advisable  in  pernicious  anaemia  rather 
than  massive  doses,  which  seem  to  overdistend  the  ves- 
sels, cause  a  marked  sense  of  discomfort,  and  stimulate 
the  new  blood  formation  rather  less  actively  than  the 
smaller  doses.  It  has  always  been  understood  that  the 
amount  of  blood  transfused  should  be  small  in  the 
presence  of  actual  bleeding  of  any  character,  intesti- 
nal or  otherwise,  where  surgical  control  is  not  feasible 
or  not  to  be  attempted.  But  these  differences  in  dosage 
are  often  veiy  gross.  An  average  size  dose,  I  should 
say,  is  about  500  c.c.  of  blood,  a  very  considerable 
amount,  and  one  that  cannot  be  given  up  or  taken  in 
without  serious  consideration  of  every  phase  of  the 


TRANSFUSION  FOR  ANAEMIA  179 

case.  Future  experience  may  teach  that  much  smaller 
doses  given  at  definite  periods  will  prove  more  effica- 
cious in  certain  conditions.  Twenty-five  cubic  centi- 
metres could  be  placed  into  a  patient's  veins  three 
times  a  day  without  the  slightest  difficulty,  now  that 
we  have  the  citrate  method  of  transfusion,  and  it  may 
be  that  a  com'se  of  such  treatment,  extending  over  a 
week  or  two,  will  come  to  be  the  routine  for  some  of 
the  angemias.  In  others,  50  c.c.  a  day  for  ten  days 
may  be  sufficient  or  100  c.c.  every  other  day,  the  idea 
being  to  use  blood  as  a  stimulant  or  perhaps  even  for 
its  nutritional  value,  instead  of  giving  it  in  bulk  as  is 
now  customary.  A  husband,  brother,  or  sister  could 
give  up  these  insignificant  amounts  of  blood  each  day, 
or  every  two  or  three  days,  without  inconvenience  or 
harm,  and  it  may  even  be  proved  that  hsemolytic  and 
agglutination  tests  will  prove  superfluous,  since  the 
amounts  given  would  be  so  small  as  to  be  incapable  of 
causing  serious  trouble. 

These  matters  are  not  capable  of  animal  experi- 
mentation, and  I  can  do  no  more  than  suggest  these 
possibilities,  leaving  it  to  the  medical  men  to  develop 
them.  The  time  has  arrived  when  we  should  seriously 
begin  to  study  blood  dosage  and  therapy.  We  must 
know  definitely  when  massive  doses  should  be  used, 
when  smaller  doses  would  be  advisable  and  when  what 
I  shall  term  therapeutic  doses  would  seem  to  be  indi- 


180  BLOOD  TRANSFUSION 

cated.  Perhaps  some  of  the  conditions  that  now  fail 
to  yield  to  the  larger  gross  doses  of  blood  might  be 
greatly  benefited  and  even  cured  by  small  therapeutic 
amounts  extended  over  a  longer  period.  There  are 
many  aspects  to  this  problem,  which  should  all  be 
investigated  and  explained.  Rapidly  as  the  advance 
in  blood  transfusion  has  taken  place,  and  brilliant  as 
the  achievements  have  been,  it  must  be  admitted  that 
some  of  its  phases  still  remain  in  a  very  misatisfactory 
state.  We  have  been  so  absorbed  with  the  technical 
details  that  others,  less  important  but  not  less  inter- 
esting, have  been  neglected. 

REFERENCES 

Bernheim,  B.  M. :  "  Therapeutic  Possibilities  of  Transfusion. 
J.  A.  M.  A.,  July  26,  1913,  vol.  Ixi,  pp.  268-270. 

Bigland,  A.  D. :  "  Fragility  of  Red  Blood  Corpuscles  in  Phy- 
siologic and  Pathologic  States."  Quarterly  Journal  of 
Medicine,  London,  July  vii.  No.  28,  1914. 

Davis,  J.  D. :  "  Influence  of  Injections  of  Blood  on  Anaemia 
and  Infections  in  Children."  Southern  Med.  Jour., 
July  ix.  No.  7,  1916. 

Libman  and  Ottenberg :  "  Blood  Transfusion ;  Indications, 
Results,  and  Management."  Am.  Jour.  Med.  Sciences, 
1916,  CI.  36-69. 

Peterson,  Edward  W. :  "  Results  from  Blood  Transfusion  in 
the  Treatment  of  Severe  Post-operative  Anaemia  and  the 
Hemorrhagic  Diseases."  J.  A.  M.  A.,  April  22,  1916, 
vol.  Ixvi. 


CHAPTER  X 
PRIMARY  PERNICIOUS  ANAEMIA 

During  the  last  two  or  three  years  much  attention 
has  been  directed  to  that  condition  known  as  primary 
pernicious  aiueinia,  and  a  voluminous  literature  has 
arisen  as  a  consequence,  all  of  which  came  about  fol- 
lowing the  investigations  of  Eppinger,  Decastello  and 
Klemperer,  who,  working  independently,  became  con- 
vinced of  the  gi-eat  good  that  might  come  from  the 
removal  of  the  spleen  in  pernicious  ansemia.  It  is 
worthy  of  note  that  Eppinger  was  led  to  adopt  this 
procedure  by  observing  after  splenectomy  a  dimin- 
ished output  of  urobilin  and  other  instances  of  de- 
creased li£emolysis,  while  Decastello  noted  the  im- 
provement that  followed  splenectomy  in  the  related 
conditions,  hsemolytic  jaundice  and  Banti's  disease. 
Klemperer  was  influenced  by  the  clinical  observation 
that  splenectomy  for  such  conditions  as  rupture  of 
the  spleen  was  in  some  instances  eventually  followed 
by  polycythemia. 

Following  the  work  of  these  three  investigators 
whose  cases  apparently  did  wondrously  well,  the  pro- 
cedm'e  of  splenectomy  was  at  once  seized  upon  almost 
throughout  the  entire  civilized  world  as  a  new  and 
successful  means  of  combating  what  had  hitherto,  been 

181 


182  BLOOD  TRANSFUSION 

considered  a  most  refractory  condition,  so  that  in  the 
short  period  of  two  and  a  half  years  a  fairly  large 
number  of  cases  has  become  available  for  study.  At 
first  certain  of  the  cases  were  splenectomized  without 
sufficient  care  in  preparation — the  operation  being 
haled  with  such  enthusiasm  that  little  consideration 
was  accorded  the  actual  surgery  necessary  to  the  re- 
moval of  the  spleen.  Many  of  these  cases,  naturally, 
promptly  died  as  a  result  of  the  operation,  whereupon 
the  custom  arose  of  either  treating  all  cases  of  per- 
nicious anaemia  by  the  usual  methods  of  drug  therapy 
until  they  were  in  a  suitable  condition  for  operation  or, 
when  this  was  not  possible,  transfusing  them  one  or 
more  times  until  such  a  state  of  affairs  came  about. 
Under  this  regime,  the  mortality  of  the  operation  has 
been  markedly  reduced  and  it  has  been  possible  to 
really  study  the  effect  that  splenectomy  might  have  on 
the  course  of  the  disease. 

Idiopathic  or  primary  progressive  anaemia  was 
characterized  by  Addison  who  first  clearly  described 
it  as  "a  general  anaemia  occurring  without  any  dis- 
coverable cause  whatever;  cases  in  which  there  had 
been  no  previous  loss  of  blood,  no  exhausting  diarrhoea, 
no  chlorosis,  no  renal,  splenic,  miasmatic,  glandular, 
strumous,  or  malignant  disease."  It  affects  middle- 
aged  persons  chiefly,  but  instances  in  young  indi- 
viduals and  in  children  have  been  described.    As  its 


PRIIVIARY  PERNICIOUS  ANAEMIA  183 

name  signifies,  it  comes  on  without  previous  illness, 
although  in  many  cases  there  is  a  history  of  gastro- 
intestinal disturbance,  mental  shock,  or  worry,  and 
(according  to  Addison)  "  It  makes  its  approach  in 
so  slow  and  insidious  a  manner  that  the  patient  can 
hardly  fix  a  date  to  the  earliest  feeling  of  languor 
which  is  shortly  to  become  so  extreme.  The  counte- 
nance gets  pale,  the  whites  of  the  eyes  become  pearly, 
the  general  frame  flabby  rather  than  wasted,  the  pulse 
perhaps  large,  but  remarkably  soft  and  compressible, 
and  occasionally  with  a  slight  jerk,  especially  under 
the  slightest  excitement.  There  is  an  increasing  indis- 
position to  exertion,  with  an  uncomfortable  feeling  of 
faintness  or  breathlessness  in  attempting  it;  the  heart 
is  readily  made  to  palpitate;  the  whole  surface  of  the 
body  presents  a  blanched,  smooth  and  waxy  appear- 
ance; the  lips,  gums  and  tongue  seem  bloodless,  the 
flabbiness  of  the  solids  increases,  the  appetite  fails, 
extreme  languor  and  faintness  supervene,  breathless- 
ness and  palpitations  are  produced  by  the  most  trifling 
exertion  or  emotion;  some  slight  cedema  is  probably 
perceived  about  the  ankles;  the  debility  becomes  ex- 
treme— the  patient  can  no  longer  rise  from  bed;  the 
mind  occasionally  wanders;  he  falls  into  a  prostrate 
and  half  torpid  state,  and  at  length  expires;  never- 
theless, to  the  very  last,  and  after  a  sickness  of  sev- 
eral months'  duration  the  bulkiness  of  the  general 


184  BLOOD  TRANSFUSION 

frame  and  the  amount  of  obesity  often  present  a  most 
striking  contrast  to  the  failm-e  and  exhaustion  ob- 
servable in  every  other  respect." 

The  red  blood-cells  show  a  progressive  decrease 
in  number  and  may  fall  to  one-fifth  or  one-tenth  of 
the  normal  number  in  extreme  cases,  while  the  haemo- 
globin falls  in  proportion,  although  this  latter  featm'e 
is  relatively  increased  as  is  indicated  by  the  color  index 
which,  in  typical  cases  of  pernicious  anaemia,  is  plus 
one,  a  condition  exactly  opposite  to  that  which  occurs 
in  secondary  anaemia,  in  which  the  corpuscular  richness 
in  coloring  matter  is  decreased,  the  color  index  being 
minus  one. 

It  has  always  been  understood,  and  in  the  light  of 
recent  investigations  correctly  so,  that  the  trouble  has 
been  the  destruction  of  the  red  cells  rather  than  a 
failure  upon  the  part  of  the  blood-forming  organs  to 
produce  those  cells  in  quantities  sufficient  to  meet  the 
needs  of  the  organism.  This  is  very  well  shown  by 
the  appearance  in  the  blood  of  those  suif ering  from 
pernicious  ansemia  of  the  characteristic  forms  of  un- 
finished blood-cells,  the  normoblasts  and  megaloblasts, 
the  presence  of  which  is  interpreted  as  indicating  a  de- 
mand upon  the  blood-forming  organs  for  red  cor- 
puscles faster  than  they  can  be  produced,  the  result 
being  that  an  incomplete  nucleated  product  is  to  a 
certain  extent  turned  loose  into  the  circulation.    As  a 


PRIMARY  PERNICIOUS  AN.EMIA  185 

rule  oiily  a  small  number  of  these  cells  are  to  be  found, 
but  upon  certain  occasions  known  as  blood  crises  they 
occur  in  myriads,  or  what  is  technically  known  as 
"  showers,"  the  exact  significance  of  which  is  obscure, 
although  it  is  commonly  considered  to  be  due  to  an 
excessive  stimulus  of  some  nature  to  the  haematopoietic 
organs. 

In  the  true  case  of  pernicious  anaemia,  the  outlook 
is  exceedingly  bad,  although  many  cases  have  been 
helped  by  treatment  with  the  various  arsenical  prepa- 
rations, some  even  coming  back  almost  to  the  normal. 
A  curious  featiu*e  always  noted  in  the  condition  is 
that  remissions  in  the  disease  not  infrequently  take 
place  of  such  character  and  unexpectedness  that 
patients  all  but  hopelessly  lost  take  on  renewed  life 
and  build  up  in  every  way  to  almost  perfect  health. 

These  remissions  are  frequently  instigated  by 
therapy,  but  it  is  a  well-known  fact  that  they  may  take 
place  absolutely  spontaneously  and  it  is  this  fact  more 
than  any  other  that  has  given  rise  to  a  certain  degree 
of  scepticism  regarding  the  benefits  to  be  expected 
from  splenectomy.  It  is  fair  to  say,  though,  that 
while  remissions  in  the  disease  are  not  at  all  common 
and  may  be  spontaneous,  after  the  occurrence  of  one 
or  two  or  three  of  them,  it  is  rare  for  another  to  come 
to  pass.  This  has  given  rise  to  a  general  sentiment 
that  if  splenectomy  offers  some  further  chance  to 


186  BLOOD  TRANSFUSION 

patients  who  have  alread}^  availed  themselves  of  the 
hoped  for  remissions  induced  by  therapeutic  measures, 
it  should  be  tried.  This  is  about  the  position  splenec- 
tomy occupies  with  regard  to  pernicious  anaemia,  at 
present. 

Blood  transfusion  was  used  in  pernicious  anaemia 
almost  as  soon  as  it  became  possible  to  do  it,  but,  as 
Crile  remarked,  the  early  cases  were  most  unsatis- 
factory because  of  the  ordeal  of  the  operation  and  the 
feeling  that  little  was  to  be  gained  by  it,  wherefore 
only  those  cases  were  submitted  for  transfusion  which 
were  practically  moribund  and  which  had  previously 
undergone  the  usual  remissions.  However,  a  few 
cases  were  reported  some  years  ago  in  which  trans- 
fusion did  help  matters.  In  1913,  I  read  a  paper 
before  the  American  Medical  Association  entitled, 
*'  Therapeutic  Possibilities  of  Transfusion,"  during 
the  course  of  which  I  mentioned  that  encouraging 
results  were  being  reported  in  pernicious  anaemia, 
although  I  suggested  that  in  this  condition  repeated 
transfusions  seemed  necessary,  and  I  reported  the  case 
of  a  man  admitted  to  the  clinic  of  Dr.  J.  C.  Bloodgood, 
who  was  transfused  four  different  times  from  three 
donors  and  lived  two  years,  after  having  been  given 
up  as  lost.  I  furthermore  said  at  this  time  that  I 
believed  that  the  "  evidence  against  transfusion  in  this 
condition  of  obscure  anaemia  is  based  on  too  few  cases 


PRIMARY  PERNICIOUS  ANEMIA  187 

and  that  until  the  number  is  great  enough  to  warrant 
accurate  deductions,  transfusions  and  repeated  trans- 
fusions should  be  practised  in  every  case  in  which 
they  would  seem  to  afford  the  slightest  chance  of  suc- 
cess. By  this  I  mean  that  the  patient  should  be 
brought  up  for  operation  before  he  is  moribund,  be- 
fore he  is  in  such  shape  that  anything  short  of  a  miracle 
could  save  him." 

Shortly  after  this,  with  the  improved  methods  of 
performing  transfusion,  more  cases  of  pernicious  anse- 
mia,  and  some  of  them  less  advanced  in  their  course, 
began  to  be  submitted  to  the  procedure  with  the  result 
that  it  soon  became  fairly  well  recognized  that  new 
blood  improved  many  patients  quite  markedly  and 
started  them  on  the  road  to  a  remission  which  often 
was  quite  prolonged.  Curiously  enough,  transfusion 
was  able  to  bring  about  a  remission  in  a  few  cases 
where  there  had  been  one  or  two  or  three  previously 
and  where  all  subsequent  efforts  to  improve  matters 
had  failed.  But  transfusion  per  se  has  never  cured 
a  case — at  least  not  to  my  knowledge — so  that  it  was 
only  natural  for  splenectomy  with  its  promised  salva- 
tion to  be  warmly  received. 

At  first,  leaving  out  of  consideration  those  few 
cases  of  ill-advised  operation,  the  results  seemed  to 
justify  all  that  was  claimed — the  down-and-out  made 
recoveries  in  many  instances  little  short  of  miraculous. 


188  BLOOD  TRANSFUSION 

Cases  in  which  there  had  been  one  and  a  half  or  two 
and  a  half  millions  of  red  cells  prior  to  operation,  a 
few  months  later  boasted  a  count  that  was  almost 
normal,  even  though  the  characteristic  blood  picture 
was  still  present  under  the  microscope. 

That  this  blood  picture  persisted  was  discouraging 
but  in  view  of  the  improved  health  of  the  patients,  it 
was  felt  that,  even  so,  much  had  been  gained.  Many 
of  the  cases  did  not  attain  to  a  real  or  approximate 
normal  count  in  point  of  numbers,  although  their 
physical  improvement  indicated  normal  blood  findings. 
In  fact,  this  has  always  been  a  remarkable  feature  of 
pernicious  ansemia  subjects;  it  has  been  astonishing 
to  note  how  well  many  of  them  could  get  along  with 
such  low  blood  counts. 

But  the  early  enthusiasm  for  the  operation  was 
doomed  to  disappointment,  because  it  was  not  long 
before  cases  which  had  done  exceedingly  well  early 
after  splenectomy  began  to  relapse,  and  as  more  and 
more  cases  were  done  and  time  progressed,  the  relapses 
became  more  frequent,  so  that  the  need  for  a  really 
comprehensive  study  of  the  whole  subject  became  most 
pressing.  This  fortune  supplied  in  the  form  of  a  paper 
read  before  the  1916  meeting  of  the  American  Medical 
Association  in  Detroit  by  Dr.  Edward  B.  Krumbhaar 
of  Philadelphia,  from  whose  report  I  am  making  ex- 
tensive references.    Out  of  a  total  of  153  cases  studied. 


PRIMARY  PERNICIOUS  AN.EMIA  18d 

30  died  within  the  first  six  weeks  after  operation,  a 
mortality  of  19.6  per  cent.  This  of  course  was  ex- 
ceedingly high,  and  perhaps  higher  than  it  is  at  the 
present  because,  as  I  stated  before,  many  cases  were 
done  at  first,  which  a  more  careful  consideration  would 
have  eliminated.  Nor  does  it  follow  that  in  20  per 
cent,  of  the  cases  some  accident  or  unforeseen  occur- 
rence happened  during  the  operation,  but  rather  that 
the  magnitude  of  the  operation,  together  with  the  low- 
ered vitality  of  many  of  the  patients,  resulted  in  thirty 
deaths  out  of  1.53  cases,  within  a  period  of  six  weeks 
after  operation.  The  mortality  at  the  present  time,  I 
would  say,  is  hardly  over  10  per  cent,  from  any  and 
all  causes. 

"  Of  the  remaining  123  patients  all  but  24  showed 
a  distinct  improvement  both  in  general  condition  and 
in  blood  picture.  Of  the  twenty-four  individuals  that 
siu-vived  the  operation,  but  failed  to  improve,  a  few 
were  obviously  harmed  by  it.  The  improvement  noted 
in  the  majority  of  cases  lasted  varying  periods.  Thus 
at  the  end  of  six  months,  of  the  53  patients  who  had 
survived  operation  for  more  than  six  weeks  and  were 
still  under  observation  at  that  time,  44  had  still  con- 
tinued to  improve  and  none  had  died,  but  nine  had 
already  relapsed.  At  the  end  of  the  first  year  after 
operation,  there  remained  27  patients  who  were  still 
under  observation,  of  which  number  the  initial  im- 


190  BLOOD  TRANSFUSION 

provement  has  been  maintained  in  less  than  half — a 
rather  discouraging  showing  when  one  takes  into  con- 
sideration the  comparatively  large  nmnber  of  cases 
under  review." 

Krumbhaar  then  goes  on  to  say,  "  Estimation  of 
the  value  of  such  a  procedure  as  splenectomy  in  per- 
nicious anaemia  must  take  into  consideration  not  only 
the  actual  results  obtained,  but  a  comparison,  as  far 
as  possible,  with  the  probable  results  if  operation  has 
not  been  undertaken.  Thus,  whereas  we  have  seen 
that  splenectomy  caused  a  quick  and  marked  improve- 
ment in  64  per  cent,  of  all  patients,  natural  remis- 
sions occm*red  at  one  time  or  another  in  80  per  cent,  of 
the  patients  of  Cabot's  series  treated  by  the  older 
conservative  methods.  One  cannot  maintain  from  this 
that  perhaps  the  improvement  after  splenectomy  was 
only  a  coincidental  remission,  because  the  onset  of 
improvement  was  too  closely  and  constantly  related 
to  the  post-operative  period;  but  it  does  offer  some 
basis  for  the  contention  that  other  methods  of  treat- 
ment may  yield  results  as  striking  as  those  following 
splenectomy.  However,  from  the  aspect  of  the  dura- 
tion of  the  disease,  the  evidence  is  more  in  favor  of  the 
splenectomized  series.  In  Cabot's  series,  almost  half 
died  in  the  first  year  of  the  disease,  and  of  the  re- 
mainder, one-third  died  in  the  next  year.  As  the  dura- 
tion of  the  disease  in  the  splenectomized  series  has 


PRIMARY  PERNICIOUS  AN^MLA  191 

already  averaged  one  and  a  half  years  before  opera- 
tion they  should  be  more  properly  compared  with  the 
remainder  of  Cabot's  group.  By  the  end  of  the  first 
year,  conditions  in  the  splenectomized  group  were  as 
follows :  Of  thirty-three  patients  surviving  the  opera- 
tion, twenty-four  were  still  improved,  three  had  failed 
to  show  improvement  or  had  relapsed  to  their  pre- 
operative condition,  and  six  had  died.  If  post-opera- 
deaths,  however,  were  to  be  included,  only  about  one- 
half  of  those  whose  fate  was  known  were  still  alive 
at  the  end  of  the  first  year.  From  both  these  points 
of  view,  therefore,  there  are  no  clear  indications  as  to 
the  value  of  splenectomy.'* 

Following  splenectomy  the  blood  changes  were 
fairly  constant,  many  cases  had  distinct  post-operative 
blood  crisis,  following  which  the  red  cell  count  and  the 
haemoglobin  began  to  rise  and  nucleated  forms  of 
cells  began  to  disappear  as  the  counts  rose.  The  color 
index,  however,  remained  high  in  nearly  every  case, 
and  no  matter  how  near  normal  the  counts  approached 
there  was  always  the  tendency  to  macrocytosis  and 
poikilocytosis,  so  characteristic  of  pernicious  anaemia. 
Those  patients  who  succumbed  early  after  operation 
showed  little  or  no  blood  changes  at  all,  except  possibly 
a  further  destruction  of  red  cells.  Of  all  the  cases 
reviewed  by  Krumbhaar,  only  five  were  living  after 
two  years,  a  most  discouraging  showing  from  certain 


192  BLOOD  TRANSFUSION 

aspects,  but  if  one  chooses  to  take  the  view  that  all 
the  cases  were  hopeless  from  the  start,  and  that  nearly 
all  of  those  operated  on  had  had  one  or  two  remissions 
prior  to  splenectomy,  and  were  therefore  doomed  to  a 
much  earlier  death,  the  evidence  is  not  quite  so  bad. 

One  point  worthy  of  careful  thought  has  been 
noted  by  all  of  those  who  have  had  any  experience 
with  splenectomy  in  pernicious  anaemia;  namely,  that 
the  best  results  follow  splenectomy  in  those  cases  that 
are  not  extremely  anaemic  at  the  time  of  operation  and 
that  have  shown  considerable  fluctuations  in  the  blood 
picture.  Simply  on  a  basis  of  common  sense  consid- 
eration, I  came  to  this  opinion  early  in  the  history  of 
this  procedure,  and  made  an  arbitrary  rule  that  no 
patient  should  come  to  operation  without  a  blood  count 
of  less  than  2,000,000  red  cells  and  a  haemoglobin  of 
less  than  30  per  cent.,  and,  acting  on  this  determina- 
tion, a  series  of  cases  done  by  Dr.  J.  M.  T.  Finney 
and  myself  have  withstood  operation  remarkably  well, 
with  one  exception,  which  will  be  mentioned  later  on. 

Krumbhaar  was  able  to  secure  information  con- 
cerning the  size  of  the  spleen  in  89  cases.  In  28  cases 
(31  per  cent.)  the  spleen  was  either  small  or  approxi- 
mately normal  in  size.  In  41  cases  (46  per  cent.) 
the  spleen  was  slightly  enlarged  and  in  20  cases  (23 
per  cent.)  it  was  considerably  enlarged.  In  other 
words,  although  seldom  palpable  before  operation,  it 


PRIMARY  PERNTCIOUS  ANAEMIA  193 

was  distinctly  enlarged  in  over  two-thirds  of  the  cases. 
If  the  results  of  splenectomy  are  subdivided  according 
to  the  size  of  the  spleen,  it  will  be  seen  that  better  post- 
operative results  were  obtained  in  the  cases  with  en- 
larged spleens. 

It  is  in  this  connection  that  I  quote  one  case 
Dr.  Finney  and  I  had,  which  failed  to  show  the  slight- 
est evidence  of  improvement  after  operation.  The 
patient  was  a  man  forty-four  years  of  age,  married, 
travelling  salesman.  He  had  the  usual  progi'essive 
course  of  pernicious  anaemia,  and  had  finally  come  un- 
der our  care  with  a  red  count  of  only  800,000  cells  and 
a  hsemoglobin  of  18  per  cent.  His  condition  was  so  pre- 
carious that  I  immediately  did  a  blood  transfusion,  in 
an  effort  to  get  him  into  shape  for  splenectomy.  A  few 
days  later  his  red  cell  count  was  1,400,000,  haemoglobin 
32  per  cent.,  but  the  blood  destroying  agencies  in  his 
circulation  were  so  active  that  within  a  week  his  count 
had  taken  a  decided  fall,  and,  curiously  enough,  his 
spleen  could  not  be  felt  nor  even  acciu*ately  located 
by  percussion.  Therefore,  in  an  almost  hopeless  effort 
to  save  him,  I  started  a  second  transfusion,  dmnng  the 
course  of  which  Dr.  Finney  removed  a  spleen  that 
was  barely  half  the  normal  size.  Two  days  after  oper- 
ation his  haemoglobin  was  24  per  cent,  and  his  red  cells 
a  little  over  1,000,000,  but  he  did  not  do  well,  was 
most  uncomfortable  and  desperately  weak,  and  within 

13 


194  BLOOD  TRANSFUSION 

a  few  days  his  hemoglobin  had  dropped  to  18  per 
cent. ;  the  reds  to  800,000  cells.  I  then  did  an  unavail- 
ing third  transfusion,  the  patient  dying  a  few  days 
later  from  a  continuous  decrease  in  the  elements  in  his 
blood,  thirty-four  days  after  splenectomy.  One  notable 
feature  of  this  case  was  that  in  spite  of  repeated  search 
there  was  hardly  a  nucleated  red  cell  to  be  seen  either 
before  or  after  splenectomy,  thus  indicating  that  at  no 
time  was  there  an  attempt  on  the  part  of  the  patient's 
bone-marrow  to  produce  new  blood.  This  case  illus- 
trates in  a  striking  manner  the  truth  of  statements 
made  by  Dr.  Krimibhaar  that  those  cases  of  pernicious 
anjemia  having  small  spleens  do  not  seem  to  do  well 
under  any  form  of  therapy.  This  is  the  only  case  in 
our  series  of  ten  in  which  we  have  found  a  definitely 
small  spleen,  and  it  is  the  only  one  where  at  least  tempo- 
rary improvement  has  not  followed  the  operation. 

As  for  the  further  benefits  of  splenectomy,  our 
own  results  agree  with  the  majority  that  the  cases 
are  remarkably  improved  for  the  time  but  invariably 
relapse.^  Sometimes  they  will  improve  under  rest  and 
arsenical  treatment  and,  in  addition  to  this,  repeated 
transfusions  seem  to  postpone  the  inevitable  end ;  but 
as  for  permanent  cure,  we  have  nothing  to  report. 

^  At  the  present  writing  I  have  just  transfused  for  the 
second  time  one  of  these  patients  who  had  her  first  relapse 
just  a  Httle  over  one  year  after  removal  of  her  spleen. 


PRIMARY  PERNICIOUS  ANAEMIA  195 

Our  most  hopeful  case  is  that  of  a  woman  who  is  now 
beginning  her  third  year,  but  whose  condition  leaves 
much  to  be  desired.^  It  is  therefore  evident  that  what- 
ever the  cause  of  the  distinct  improvement  after  sple- 
nectomy, simple  removal  of  the  spleen  does  not  remove 
the  cause  of  the  disease.  It  seems  rather  that  a  major 
destroying  force  has  been  removed  from  the  circula- 
tion without  whose  continual  irritation  the  bone-mar- 
row is  able  to  produce  blood-cells.  It  is  conceivable 
that  the  relapse  subsequent  to  splenectomy  is  due  to 
lisemolymph-nodes,  accessory  spleens  and  even  the 
liver  taking  over  the  functions  of  the  spleen,  although 
this  has  not  been  definitely  proved. 

Finally,  it  is  proper  to  consider  just  what  are  the 
indications  for  splenectomy  in  pernicious  ansemia. 
According  to  Krmnbhaar,  "  One  or  two  lines  may  be 
followed  and  it  is  as  yet  early  to  say  which,  if  either, 
is  correct.  If  splenectomy  merely  induces  a  remis- 
sion, and  this  is  at  present  the  opinion  of  the  majority 
of  observers,  it  would  be  logical  to  undertake  it  only 
as  a  last  resort,  when  all  other  measures  have  proved 
unavailing  and  only  with  the  hope  of  prolonging  life. 
Even  under  such  limitations,  however,  the  procedure 
has  already  proved  its  value,  and  in  several  cases 

2  This  patient  has  just  recently  survived  an  operation 
for  ruptured  appendix  with  widespread  peritonitis. 


196  BLOOD  TRANSFUSION 

moribund  patients  have  been  brought  back  to  a  life  of 
comparative  well-being  for  many  months.  Assuming, 
on  the  other  hand,  that  an  occasional  patient  may  be, 
for  practical  purposes,  cured  of  the  disease,  and  giving 
due  weight  to  the  view  that  greater  and  longer  con- 
tinued improvement  is  obtained  if  the  operation  is 
performed  before  the  disease  has  reached  its  final 
stage,  it  would  then  be  advisable  to  undertake  it  as 
soon  as  possible.  Another  factor  that  may  prove 
to  be  decisive  is  whether  or  not  increased  haemolysis 
can  be  proved.  In  those  cases  with  clinically  enlarged 
spleen,  icteroid  appearance,  and  increased  urobilin  out- 
put, without  increased  resistance  of  the  erythrocytes, 
the  prognosis  is  distinctly  more  favorable  than  in  the 
opposite  types.  The  condition  of  the  bone-marrow  is 
also  important,  splenectomy  being  contra-indicated  if 
the  bone-marrow  is  persistently  aplastic.  It  has  also 
been  a  matter  of  clinical  observation  that  those  indi- 
viduals in  whom  spinal  cord  symptoms  have  already 
developed  are  less  apt  to  be  helped  by  the  operation." 
In  summarizing  this  chapter  on  pernicious  anaemia, 
I  can  perform  no  better  ser\'ice  than  by  giving  the 
conclusions  reached  by  Dr.  Krumbhaar  in  toto,  since 
his  study  has  been  critical  and  fair-minded,  and  his 
findings  have  agreed  so  thoroughly  with  those  reached 
independently  by  nearly  everyone  who  has  been  en- 
gaged in  the  actual  clinical  study  and  treatment  of 


PRIMARY  PERNICIOUS  ANEMIA  197 

pernicious  ansemia.    These  conclusions  are  as  follows : 

1.  Of  the  153  patients  studied,  19.6  per  cent,  died 
within  six  weeks ;  a  distinct  improvement  in  the  clinical 
condition  and  in  the  blood  picture  occurred  in  64,7 
per  cent.,  and  no  improvement  in  15.7  per  cent. 

2.  The  rather  high  post-operative  mortality  (prac- 
tically 20  per  cent.)  may  be  due  to  poor  choice  of 
cases  in  the  early  series.  As  a  much  greater  propor- 
tion of  the  more  recent  cases  has  survived  the  opera- 
tion, the  true  post-operative  mortality  is  probably 
much  less  than  20  per  cent. 

3.  Of  the  individuals  who  showed  improvement 
shortly  after  operation,  nearly  two-thirds  of  the  total 
number,  a  large  number  have  failed  to  maintain  this 
improvement,  or  have  since  died  in  a  relapse  or  from 
intercurrent  disease. 

4.  Although  a  few  have  continued  in  good  con- 
dition during  the  period  of  observation  (over  two 
years),  in  no  case  can  it  be  said  that  a  cure  has  been 
effected,  and  the  blood  of  these  individuals  continues 
to  show  many  of  the  characteristic  signs  of  pernicious 
ansemia. 

5.  On  account  of  the  improvement  that  follows 
splenectomy,  it  would  appear  to  be  not  only  a  justi- 
fiable, but  in  many  cases  an  advisable,  procedure; 
but  in  no  case  shoidd  a  cure  be  promised  or  the 
operation  undertaken  except  under  the  most  f  a^'^orable 
conditions. 


198  BLOOD  TRANSFUSION 

6.  The  best  results  are  obtained  if  the  operation 
is  preceded  by  one  or  more  transfusions,  and  those 
patients  who  relapse  after  operation  may  still  be 
greatly  helped  by  transfusion.  Whether  or  not  trans- 
fusion would  have  produced  equally  good  results  in 
the  absence  of  splenectomy  is  a  question  that  cannot 
at  present  be  decided. 

7.  The  most  favorable  results  may  be  expected  in 
individuals  who  have  not  passed  the  fifth  decade,  in 
whom  the  disease  has  not  progressed  for  more  than  a 
year,  and  who  have  a  relatively  good  blood  picture 
(that  is,  an  anaemia  that  is  not  of  too  extreme  a  degree 
or  of  the  steady,  progressive  type) .  Individuals  with 
enlarged  spleens  have  done  better  than  those  in  whom 
the  spleen  was  small  or  of  normal  size,  as  have  also 
those  suffering  from  an  ansemia  characterized  by  ex- 
cessive haemolysis. 

8.  The  opposite  of  these  conditions  should  be  con- 
sidered as  unfavorable  factors,  as  should  also  the  ex- 
istence of  spinal  cord  symptoms  or  the  presence  of  an 
aplastic  bone-marrow. 

REFERENCES 

Balfour,  Donald  C. :  "  Indications  for  Splenectomy  in  Cer- 
tain Chronic  Blood  Disorders — the  Technic  of  the 
Operation."  J.  A.  M.  A.,  September  9,  1915,  vol.  Ixvii, 
pp.  790-793. 


PRIIVIARY  PERNICIOUS  ANAEMIA  199 

Decastello,  A. :  "  Ueber  den  Einfluss  der  Milzexstirpation 
auf  die  pemiziose  Anamie."    Deut.  Med.  Woch.,  1914. 

Etppinger,  Hans,  and  Ranzi,  Egon:  "  Indicationen  und  Re- 
sultate  der  Splenektomie."  Cent.  f.  CJUr.,  No.  52,  p. 
2004,  1913. 

Eppinger,  H. :  "  The  Spleen  in  Pernicious  Anamia  (Zur 
Pathologic  der  Mik-funktion  II)."  Berliner  Kim. 
Wochenschr.,  December  29,  1914. 

Huber,  D.  R.  C. :  "  Einfluss  der  Milzexstirpation  bei  perni- 
cioser  Anemia."  Berliner  Klin.  Wochenschrift,  Novem^ 
ber  24,  1913,  No.  47. 

Klemperer,  G.,  and  Hirschfeld:  "  Splenectomiy  in  Treatment 
of  Pernicious  Anaemia."  Therapie  der  Gegenwart^  Sep- 
tember, 1913,  liv.  No.  9,  pp.  385-432. 

Krumbhaar,  Edward  B. :  "  Late  Results  of  Splenectomy  in 
Pernicious  Anaemia."  J.  A.  M.  A.,  September  2,  1916, 
vol.  Ixvii,  pp.  723,  727. 

Lee,  Roger  I.;  Vincent,  Beth,  and  Robertson,  Oswald: 
"  Immediate  Results  of  Splenectomy  in  Pernicious 
Anaemia."    J.  A.  M.  A.,  July  17,  1915,  vol.  Ixv. 

McClure,  Roy  D. :  "  Pernicious  Anaemia  Treated  by  Splenec- 
tomy and  Systematic,  Often-Repeated  Transfusion  of 
Blood.  Transfusion  in  Benzol  Poisoning."  J.  A.  M.  A., 
September  9,  1916,  vol.  Ixvii,  pp.  793-796. 

Moffitt,  H.  C. :  "  Studies  in  Pernicious  Anaemia."  Am.  Jour- 
nal of  Medical  Sciences. 

Musser,  J.  H.,  and  Krumbhaar,  E.  B. :  "  Relation  of  Spleen 
to  Blood  Destruction  and  Regeneration  to  Haemolytic 
Jaundice.  The  Blood-picture  at  Various  Periods  after 
Splenectomy."  Journal  of  Exper.  Med.,  November  5, 
1913. 


200  BLOOD  TRANSFUSION 

Roblee,  W.  N. :  "  Splenectomy  in  Primary  Perniciaus  Anae- 
mia." J.  A.  M.  A.,  March  6,  1915. 
Turk,  W :  "  Bedeutung  der  Milz  bei  anamischen  zu-standen 

in  Bezug  auf  Pathogenese  and  Therapie.*'   Deut.  Med. 

Woch.,  February  19,  1914,  xl,  No.  8. 
Vander  Hoof,  Douglas :    "  Jaundice  in  Pernicious  Anaemia." 

Domimon  Journal  of  Medicine  and  Surgery,  vol.  xii, 

No.  4,  April,  1911. 
Vogel,  K.  M.,  and  McCurdy,  U.  F. :    "  Blood  Transfusion 

and  Regeneration  in  Pernicious  Anaemia."     Archives  of 

Int.  Medicine,  December,  1913. 
Vogel,  Karl  M. :  "  Theories  of  the  Etiology  of  Anaemia." 

J.  A.M.  A.,  April  1,  1916. 


CHAPTER  XI 

TRANSFUSION  FOR  HAEMOPHILIA,  MEL^NA  NEO- 
NATORUM, PURPURA,  JAUNDICE 

No  more  interesting  group  of  diseases  is  to  be 
found  than  that  of  the  so-called  hemorrhagic  diseases, 
nor  is  there  a  group  which  presents  for"  solution  a  more 
intricate  set  of  problems,  since  under  this  heading  are 
to  be  found  a  number  of  different  morbid  conditions, 
having  in  common  the  one  element  of  bleeding.  The 
blood  loss  varies  in  location  and  severity  from  in- 
significant cutaneous  hemorrhages  in  mild  cases  of 
purpura  to  appalling  and  even  fatal  hemorrhages  in 
the  more  serious  types  of  these  affections. 

According  to  Moss  and  Gelien,  "An  enumeration 
of  the  diseases  in  which  hemorrhage  is  or  may  be  asso- 
ciated, and  which  are  sometimes  designated  hemor- 
rhagic diseases  includes: 

"  Hsemophilia,  hereditary  and  spontaneous. 

"  Hemorrhagic  diseases  of  the  newborn,  of  which 
there  are  doubtless  several  forms. 

"  Purpuras,  acute,  chronic,  simple,  rheumatic, 
senile,  etc. 

"  Jaundice. 

"  Grave  anasmias. 

201 


«02  BLOOD  TRANSFUSION 

"  A  heterogeneous  group,  including  nephritis, 
typhoid  and  other  severe  infections." 

It  is  unnecessary,  for  the  purposes  of  this  mono- 
graph, to  enter  upon  a  discussion  concerning  the  eti- 
ology of  these  various  conditions,  especially  since  there 
is  such  profound  obscurity  and  so  many  contradictions 
regarding  them  that  it  could  not  be  profitable.  Those 
interested  are  referred  to  special  articles.  But  since 
hemorrhage  is  their  common  feature,  and  the  one  ele- 
ment that  concerns  us  because  of  its  danger,  and  since 
this  bleeding  is  of  spontaneous  character  and  most 
refractory  from  every  standpoint,  we  pause  to  note 
that  a  defect  in  the  coagulation  apparatus  of  the 
blood  is  considered  to  be  present  in  each  of  the  various 
conditions.  This,  of  coiu*se,  is  the  common-sense  view- 
point, foi'how  else  could  spontaneous  bleeding  occur? 
Opinions  differ  in  regard  to  the  element  of  coagu- 
lation lacking,  and  in  regard  to  the  cause  of  the  de- 
ficiency whatever  it  may  be,  >some  inchning  to  the 
belief  that  it  is  an  infection  of  an  obscure  order,  others 
that  it  is  a  developmental  deficiency  in  the  make-up 
of  the  blood  or  tissue  of  those  afflicted,  perhaps  of 
hereditary  origin.  Evidence  is  accumulating,  however, 
which  influences  the  belief  that  some  forms  are  the 
result  of  infection,  while  others  present  developmental 
deficiencies  of  a  serious  order.  Of  this  latter  type,  the 
most  striking  example  is  to  be  found  in  haemophilia, 


FOR  HEMORRHAGIC  DISEASES  203 

in  which  condition  Howell  has  clearly  demonstrated 
that  the  fault  is  to  be  found  in  a  lack  of  prothrombin, 
one  of  the  elements  necessary  to  the  coagulation  of 
blood. ^  Thus  it  may  very  well  come  to  pass  that  the 
various  disease  entities  will  be  found  to  differ  only 
in  the  radicle  of  the  coagulation  apparatus  that  is  ab- 
sent, though  much  work  remains  to  be  done  before 
anything  of  a  definite  nature  can  be  said. 

Haemophilia  is  perhaps  the  best  known  member 
of  the  group  of  hemorrhagic  diseases  because  of  its 
distressing  character  and  its  peculiarly  deadly  nature. 
Without  question  many  so-called  "  bleeders  "  reach 
maturity,  but  it  is  doubtful  if  many  of  them  live  an 
ordinary  span  of  life — the  gi'eat  majority  die  within 
the  first  few  years  or,  surviving  these,  pass  through 
numerous  harrowing  experiences,  only  to  succumb  in  a 
culminating  attack  more  terrible  than  any  previous. 
Very  possibly  the  conditions  may  be  outgrown  in  a 
few  instances,  thus  accounting  for  the  fact  that  bleeders 
are  rarely  seen  among  those  who  have  passed  early 
adult  life. 

The  pathogenesis  of  the  condition  remains  obscure. 
According  to  Howell  a  deficient  amount  of  prothrom- 
bin is  found  in  the  blood,^  while  Morawitz  accounts 
for  the  bleeding  by  a  lack  of  thrombokinase.     Both 

^  See  Chapter  I  for  Howell's  theory  of  coagulation. 


M4  BLOOD  TRANSFLSION 

theories  have  their  adherents,  but  the  trend  of  opinion 
rather  seems  to  favor  Howell's  view.  According  to 
Hess,  "  the  plasma  of  the  haemophiliac  has  a  delayed 
clotting  time,  varying  generally  from  about  one-half 
hour  to  many  hours,"  which  explains  the  prolonged  in- 
tractable bleeding  associated  with  the  condition  in  cases 
of  accidental  wounds.  It  is  well  to  note,  though,  that 
marked  variations  in  coagulation  time  are  quite  fre- 
quently found  in  recognized  cases  of  hemophilia — espe- 
cially after  some  previous  hemorrhage,  when,  as  first 
mentioned  by  Sahli,  instead  of  the  blood  being  delayed 
in  its  coagulation,  a  very  rapid  clotting  may  take  place. 
No  explanation  has  been  forthcoming  for  this  peculiar 
phenomenon. 

Cellular  examination  of  haemophiliac  blood  reveals 
nothing  unusual,  even  the  platelet  count,  as  shown  by 
Duke,  Hess  and  others,  being  normal.  This  latter 
finding,  though,  is  of  interest  and  aid  in  differentiating 
hcemophUia  from  purpura,  where  the  platelet  count  is 
usually  found  quite  low.  Still  another  point  in  differ- 
entiating the  two  conditions  is  the  so-called  "  bleeding- 
time,"  by  which  is  meant  the  tendency  to  bleed  from  a 
puncture  wound,  such  as  is  made  by  a  hypodermic 
needle.  The  bleeding  time  is  considered  to  be  about 
normal  in  haemophilia,  but  increased  in  purpura. 

It  is  unnecessary  to  dwell  at  any  length  upon  the 
clinical  course  of  the  condition,  since  it  is  quite  familiar 


FOR  HEMORRHAGIC  DISEASES  205 

to  all  medical  men  and  even  to  a  great  proportion  of 
the  laity.  The  common  story  is  that  the  patient  has 
received  a  small  cut  or  abrasion,  usually  of  an  insignifi- 
cant nature,  but  in  spite  of  the  ordinary  home  remedies, 
bleeding  has  not  ceased.  Since  the  condition  is  gen- 
erally of  a  hereditary  character,  it  is  possible  in  the 
vast  majority  of  instances  to  obtain  a  characteristic 
history,  although  I  have  occasionally  been  confronted 
with  the  story  that  the  case  in  hand  was  the  first  one 
ever  noticed  in  the  family.  One  can  readily  under- 
stand the  importance  of  securing  accurate  knowledge 
on  this  subject,  because  of  the  necessity  for  instituting 
proper  therapeutic  measures.  Not  infrequently  cases 
of  protracted  ooze  are  encountered  where  the  condi- 
tion is  by  no  means  one  of  haemophilia,  and  the  ordinary 
surgical  measures,  properly  used,  suffice,  whereas,  if  a 
definite  story  of  haemophiha  is  obtained,  not  only  must 
the  aid  of  the  usual  surgical  measures  be  invoked,  but 
preparations  should  be  made  without  delay  for  certain 
additional  measures. 

Briefly,  the  treatment  of  haemophilia  resolves  itself 
into  the  following  steps : 

1.  Reassuring  of  the   patient   and  the  patient's 
family  if  possible. 

2.  Absolute  rest  and  quiet  for  the  patient. 

3.  A  snug  bandage  over  the  wound  surface. 

4.  A  few  drops  of  fresh  human  tissue  juice  over 


«06  BLOOD  TRANSFUSION 

the  wounded  area,  if  ordinary  surgical  measures  such 
as  pressm*e,  ligation  of  bleeding  points,  etc.,  will  not 
stop  the  bleeding.  If  tissue  cannot  be  secured  a  few 
drops  of  fresh  human  blood  may  be  dropped  on  the  sur- 
face, or  preferable  to  blood,  human  senmi  may  be  used. 
5.  Thirty  c.c.  of  human  serum^  may  be  injected 
subcutaneously,  or  fifteen  c.c.  of  it  may  be  given  intra- 
venously. In  lieu  of  the  fresh  human  serum,  subcu- 
taneous injection  of  fresh  human  blood  may  be  used, 
or,  if  nothing  from  the  human  is  obtainable,  animal 
serum,  such  as  horse  serum  or  rabbit  serum,  may  be 
used.  The  serum  therapy  of  this  and  allied  conditions 
has  been  advocated  chiefly  by  Weil,  whose  reported 
results  were  quite  good.  Unfortunately,  later  obser- 
vations by  other  workers  along  similar  lines  show  that 
the  efficacy  of  serum  in  checking  the  bleeding  encoun- 
tered in  haemophilia  and  the  other  members  of  the 
hemorrhagic  group  of  diseases,  has  been  regarded  witli 
a  little  too  much  optimism.  The  present  view  concern- 
ing the  matter,  and  I  think  it  is  the  common-sense 
view,  is  that  at  the  initial  stage  of  haemophiliac  or  any 
other  intractable  bleeding,  the  aid  of  serum  should  be 
invoked.  If  a  cessation  comes  about,  all  is  well  and 
good.  If  not,  and  all  other  measures  have  failed,  it  is 
wise  to  proceed  without  delay  to  the  last  resort  which  is 

^  Calcium  salts  have  been  found  practically  worthless. 


FOR  HEMORRHAGIC  DISEASES  207 

6.  Blood  Transfusion. — Noraial  human  blood,  of 
course,  has  all  the  requirements  for  normal  coagulation, 
and  since,  as  noted  above,  one  of  these  requirements, 
namely,  prothrombin,  is  lacking  in  the  blood  of  haemo- 
philiacs, it  is  but  natural  to  suppose  that  the  intravenous 
introduction  of  whole  blood  will  bring  about  at  least  a 
temporary  coagulation.  And  so  it  does  clinically.  It  has 
even  been  suggested  since  this  is  so,  that  every  person 
known  to  be  suffering  from  haemophilia  should  be  ad- 
vised of  his  blood  group,  and  that  he  should  have  the 
names  and  addresses  of  several  individuals  of  that 
group,  who  would  be  available  upon  a  moment's  notice, 
and  would  be  willing  to  supply  him  with  serima  or 
blood  in  case  of  need.  So  far  as  my  experience  with 
the  condition  goes,  a  very  small  amount  of  transfused 
blood  will  bring  about  an  almost  immediate  cessation 
of  the  bleeding,  but  of  course  the  dosage  must  depend 
to  a  great  extent  on  the  actual  blood  lost  before  the 
transfusion.  For  cases  of  tremendous  blood-loss  it  is 
not  sufficient  to  merely  insure  coagulation,  but  the 
consequent  anaemia  must  be  relieved.  I  sometimes  feel 
that  the  adherents  of  the  serum  therapy  allow  their 
enthusiasm  to  overcome  their  saner  judgment  when, 
in  the  face  of  continuous  bleeding,  they  persist  in  giv- 
ing repeated  doses  of  serum.  If  two  or  three  doses 
of  serum  fail  to  give  results  after  a  reasonable  period, 
it  is  unlikely  that  larger  quantities  will  achieve  any 


«08  BLOOD  TRANSFUSION 

better  results,  so  preparations  for  transfusion  should 
be  made  and  intravenous  blood  given  without  delay. 
In  this  way  not  only  will  many  lives  be  saved,  but  the 
dose  of  blood  required  will  be  hardly  over  100  or  200  c.c. 

Not  many  months  ago,  late  at  night,  I  saw  a  little 
babj^  who  had  been  circumcised  six  hours  before.  Pre- 
vious to  my  arrival  two  attempts  had  been  made  to 
stop  the  ooze  by  suturing,  but  without  success.  The 
child  was  in  very  good  condition,  so  I  tried  to  stop  it  by 
placing  additional  sutures,  also  unavailing.  The  story 
was  that  an  older  brother  had  suffered  a  very  severe 
hemorrhage  after  circimicision  but  had  recovered.  A 
sister,  born  one  year  before,  had  bled  to  death  from  an 
obscure  form  of  vaginal  bleeding.  The  father  and 
mother  were  healthy,  rather  intelligent  people,  but  had 
never  even  heard  of  anything  like  hsemophilia.  The 
case  seemed  reasonably  clear  cut  to  me,  so  I  immedi- 
ately administered  to  the  child  55  c.c.  of  citrated  blood 
from  its  father.  The  bleeding  ceased  immediately,  and 
the  child  made  an  uneventful  recovery.  In  this  case 
no  serum  was  given.  It  was  considered,  but  since  trans- 
fusion is  simple  and  is  surer  in  its  results  than  serum, 
and  since  the  child  was  in  the  hospital,  I  felt  that 
transfusion  was  the  preferable  measure. 

Very  recently.  Dr.  William  H.  Howell,  of  the 
Johns  Hopkins  University,  has  produced  a  substance 
known  as  Kephalin,  which  is  made  of  brain  tissue  of 
the  hog.    It  was  his  idea  to  secure  an  extract  of  that 


FOR  HEMORRHAGIC  DISEASES  «09 

tissue  most  active  in  stimulating  blood  coagulation,  and 
since  his  experiments  showed  that  the  highly  cellular 
brain  was  richest  in  activating  properties,  its  tissue 
was  chosen.  Kephalin,  which  is  now  on  the  market,^ 
can  be  obtained  in  any  desired  quantity,  is  especially 
efficacious  if  it  can  be  applied  directly  to  the  bleeding 
point,  and  held  in  place  either  by  bandage  or  other 
means.  Not  only  is  it  of  service  in  hsemophilia,  but 
quite  recently  Dr.  H.  L.  Cecil,  of  the  Brady  Clinic, 
reported  most  satisfactory  results  after  its  use  in  cer- 
tain of  the  operations  done  in  the  Genito-Urinary 
Department  of  the  Johns  Hopkins  Hospital.  The 
method  of  procedure  there  is  to  use  kephalin  impreg- 
nated gauze  for  packing  purposes  or  to  make  an  ether 
solution  of  kephalin,  dip  sound  or  catheter  into  it, 
and  allow  this  to  remain  in  place  over  a  wound  area 
such  as  follows  the  "  punch  "  operation  for  prostatic 
obstruction. 

Dr.  Howell  himself  has  been  able  to  stop  subcu- 
taneous bleeding  in  several  cases  of  haemophilia  by 
feeding  kephalin,  but  further  trial  must  be  made  be- 
fore definite  results  can  be  claimed  for  this  method. 
However,  with  serum  therapy,  fresh  tissue,  kephalin, 
and  finally  blood  transfusion,  the  fortune  of  those 
afflicted  with  haemophilia  seems  at  least  a  little  rosier 
than  it  did  a  few  years  ago. 

^  It  is  made  by  Hynson,  Westcott  &  Dunning,  of  Balti- 
more, also  by  Armour,  of  Chicago. 
14 


210  BLOOD  TRANSFUSION 

Melcena  Neonatorum. — This  term  is  applied  to 
those  instances  of  hemorrhage  in  the  new-bom,  where 
shortly  after  birth — at  times  within  twenty-four  or 
thirty-six  hours,  earlier  or  later,  spontaneous  bleed- 
ing arises  of  an  unknown  origin.  It  usually  comes 
from  some  part  of  the  alimentary  tract  and  is 
manifested  by  bloody  stools,  though  at  times  it  may 
come  from  the  umbilicus  or  appear  in  the  form  of 
widespread  subcutaneous  hemorrhages  while,  in  rarer 
instances,  a  combination  may  be  present.  The  bleed- 
ing is  alwaj^s  most  dangerous  because  of  its  intracta- 
bility and  because  of  the  fact  that  the  subjects  have 
so  little  blood  to  lose.  The  parents  of  these  infants 
are  practically  always  perfectly  normal  in  every  re- 
spect, and  the  delivery  apparently  has  nothing  at  all 
to  do  with  the  condition,  which  may  occur — in  fact 
usually  does — in  one  child  and  not  in  its  brothers  and 
sisters.  Syphilis  is  supposed  to  be  the  cause  in  some 
cases,  especially  in  those  associated  with  bleeding  from 
the  imabilicus,  and  an  obscure  form  of  general  infec- 
tion is  believed  to  be  responsible  for  the  remainder,  an 
opinion  unsustained  by  proof. 

The  mortality  approaches  100  per  cent,  in  un- 
treated cases,  and  all  cases  may  be  said  to  have  been 
imtreated,  so  far  as  practical  results  were  concerned, 
until  Carrel  of  the  Rockefeller  Institute  carried  out 
a  successful  blood  transfusion  in  the  case  of  an  infant 


FOR  HEMORRHAGIC  DISEASES  211 

exsanguinated  from  this  condition.  This  was  in  1908 
and  the  case,  reported  by  Dr.  S.  W.  Lambert,  marks 
an  epoch  of  the  most  startling  character  in  the  annals 
of  blood  transfusion,  for  since  that  time  hundreds  of 
patients  suffering  from  this  and  allied  conditions  have 
been  saved  by  means  of  transfusion,  while  previously 
all,  or  practically  all,  had  been  lost. 

Until  recently  little  babies  have  offered  a  most 
formidable  problem  in  transfusion  because  of  inherent 
difficulties  encountered  in  working  with  them,  so  that 
great  enthusiasm  prevailed  when  Welch  reported  that 
he  had  cm-ed  12  cases  of  melaena  neonatorum  by  subcu- 
taneous injections  of  fresh  human  serum,  his  average 
dose  being  80  c.c.  in  10-c.c.  doses  extending  over  a 
period  of  four  days,  but  in  exceptional  cases  209  c.c.  in 
five  days.  When  Schloss  in  the  following  year  reported 
that  whole  blood  injected  subcutaneously  could  be  used 
in  place  of  serum,  which  at  times  might  be  difiicult 
to  secure  or  at  least  would  necessitate  a  delay,  the 
difficulty  was  thought  to  be  overcome. 

As  in  the  case  of  so  many  other  forms  of  therapy, 
early  reports  were  a  bit  exaggerated  and  subsequent 
investigations  necessitated  a  certain  amount  of  quali- 
fication in  the  claims  of  subcutaneous  serum  and  blood. 
They  do  most  certainly  stop  the  bleeding  in  many  of 
the  cases  but  they  do  not  succeed  in  a  considerable 
proportion,  for  some  unexplained  reason.    So  that,  as 


212  BLOOD  TRANSFUSION 

matters  now  stand,  it  is  advisable  to  give  a  subcutane- 
ous injection  of  15  or  20  c.c,  or  30  or  40  c.c.  of  whole 
blood  at  the  inception  of  every  case  of  bleeding  in 
the  new-bom,  and  if  the  desired  cessation  does  not 
appear  within  an  hour,  or  two,  to  resort  to  transfusion 
of  blood  without  delay,  the  amount  of  blood  transfused 
being  anywhere  from  35  to  90  c.c.  or  even  125  c.c. 
where  there  is  severe  exsanguination. 

A  ease  in  point  is  one  I  did  in  January,  1916.  A 
baby  thirty-six  hours  old,  delivery  perfectly  normal, 
suddenly  began  to  pass  blood  from  the  bowel,  and 
four  hours  later  was  given  15  c.c.  of  human  serum 
subcutaneously.  In  spite  of  this,  it  continued  to  have 
bloody  stools,  and  a  few  hours  later  showed  signs  of 
collapse,  whereupon  I  injected  45  c.c.  of  blood  into  its 
internal  jugular  vein,  its  father  serving  as  donor. 
Bleeding  ceased  immediately  and  the  child  made  a 
perfect  recovery. 

The  efficacy  of  transfusion  in  this  condition  became 
apparent  before  indirect  transfusion  was  available  as 
a  practical  method  and  one  can  imagine  what  a  difficult 
matter  it  was  to  unite  by  means  of  a  cannula  an  adult's 
radial  artery  to  a  twenty-four  or  thirty-six  hour  old 
infant's  femoral  vein,  or  even  its  external  jugular  vein, 
as  was  suggested  by  Beth  Vincent.  In  fact,  it  was  an 
all-night  struggle  in  just  such  a  case — the  result  of 
which  was  fortunately  successful — ^that  gave  me  the 


FOR  HEMORRHAGIC  DISEASES  21S 

idea  of  the  two-piece  transfusion  tube  that  I  devised 
in  1910.  This  simplified  matters  a  good  deal,  but  the 
needle  and  syringe  method  of  Lindeman  came  along 
shortly  afterwards  and  solved  most  of  the  difficulties. 
Even  this  offered  problems,  because  a  vein  had  to  be 
isolated,  and  veins  of  infants  are  neither  easy  to  isolate 
nor  satisfactory  to  work  with  after  preparation  be- 
cause of  their  delicacy  and  smallness.  The  whole 
matter  was  then  settled  by  Helmholtz  of  Chicago,  who 
showed  that  blood  might  be  injected  into  the  longi- 
tudinal sinus  of  these  infants  with  great  ease  and 
without  danger.  It  seems  therefore  that  since  senmi 
will  stop  the  bleeding  in  only  a  certain  percentage  of 
the  cases  and  transfusion  in  practically  all,  the  latter 
form  of  therapy,  which  is  so  simple  to  perform  that  it 
is  hardly  more  complicated  than  a  subcutaneous  injec- 
tion of  whole  blood  or  serum  should  be  the  method  of 
choice.* 

To  summarize,  then,  melcena  neonatorum  is  an 
obscure  form  of  intestinal  bleeding  in  the  new-born 
which  is  always  dangerous.  It  is  the  one  member  of 
the  so-called  hemorrhagic  group  of  diseases  which  is 
known  to  be  cured,  once  cessation  of  the  bleeding  is 
attained.    Subcutaneous  injection  of  serum  will  cause 

*  I  think,  however,  that  extreme  care  should  be  exerted  in 
this  procedure  because  of  the  ease  with  which  the  sinus  wall 
could  be  punctured. 


ei4  BLOOD  TRANSFUSION 

cessation  in  a  certain  proportion  of  cases,  subcutane- 
ous injection  of  whole  blood  will  cause  a  cessation  per- 
haps in  a  smaller  proportion,  while  transfusion  of 
blood  will  stop  the  bleeding  in  practically  every  case 
if  carried  out  early  enough.  It  is  permissible  to  try 
serimi  or  subcutaneous  blood  at  the  beginning  of  all 
cases  of  bleeding,  but  where  prompt  cessation  does  not 
follow,  transfusion  should  be  performed  without  delay. 
Where  the  bleeding  has  continued  without  treatment 
for  any  length  of  time,  simple  control  is  not  sufficient, 
since  the  blood  loss  should  be  made  up  by  transfusion. 
Finally,  in  view  of  the  recent  simple  method  of  inject- 
ing blood  into  the  longitudinal  sinus  as  suggested  by 
Helmholtz,  it  seems  wise  to  transfuse  every  case  as 
soon  as  it  starts,  rather  than  run  the  risk  of  failing  to 
control  the  bleeding  by  the  use  of  serum. 

Purpura, — By  this  term  is  understood  those  bleed- 
ings of  spontaneous  and  obscure  origin  that  occur  into 
the  tissues.  They  may  be  subcutaneous,  into  the 
joints,  into  the  deeper  tissues,  or  the  bleeding  may 
become  manifest  by  an  intestinal  seepage  of  a  most 
intractable  character.  It  is  usually  considered  that 
purpura  is  due  to  some  bacterial,  metabolic,  or  chemi- 
cal toxaemia,  and  for  each  theory  certain  substantia- 
tion has  been  found,  such,  for  instance,  as  the  sub- 
cutaneous hemorrhages  encountered  in  the  recognized 
septicaemias  in  support  of  the  bacterial  theory.    But, 


FOR  HEMORRHAGIC  DISEASES  215 

withal,  the  etiology  is  as  obscure  and  unsatisfactory 
as  is  the  therapy,  and  we  are  confronted  with  a  danger- 
ous recurrent  disease  which  arises  spontaneously,  and 
occasionally,  though  not  often,  disappears  spontane- 
ously— and  most  mysterious  of  all,  repeated  examina- 
tions by  many  different  investigators  have  yet  to  re- 
veal the  slightest  abnormality  in  the  blood  picture 
except  a  diminuition  or  total  absence  of  platelets  as 
noted  by  Duke,  and  confirmed  by  later  investigators. 

Platelets  are  supposed  to  have  a  fundamental  in- 
fluence on  blood  coagulation  and  their  absence  from  the 
blood  might  well  account  for  the  subcutaneous  hemor- 
rhages and  the  long  continued  bleedings  encountered  in 
purpuric  conditions.  But  what  causes  the  platelets  to 
be  absent  and  are  they  destroyed  after  being  formed 
or  are  they  never  made  in  this  condition?  Purpuric 
spots  and  bleedings  are  but  symptoms  of  an  under- 
lying condition,  and  an  absence  of  platelets  only  ex- 
plains the  occurrence  of  the  symptoms.  By  no  means 
does  this  feature  shed  light  on  the  etiologj% 

As  a  result  some  men  consider  the  basic  condition 
to  be  due  to  an  inherent  defect  in  the  blood-vessel 
wall  which  under  certain  conditions,  unexplained  thus 
far,  permits  the  blood  to  escape  from  its  confines 
into  the  surrounding  tissues  in  the  form  of  the  so- 
called  purpuric  spots.  A  fanciful  explanation,  per- 
haps, but  one  held  by  such  a  well-known  investigator 
as  Sahli  of  Switzerland. 


216  BLOOD  TRANSFUSION 

Whatever  the  underlying  cause,  the  condition  is 
always  to  be  regarded  with  concern  because  of  the 
possibilities  for  trouble.  Encountered  in  people  of  all 
ages,  most  cases  are  mild  and  yield  to  rest,  diet,  and 
the  usual  forms  of  therapy  used  for  conditions  of 
supposedly  disturbed  metabolism,  while  those  cases 
which  occur  during  the  course  of  a  recognized  disease 
or  infection,  usually  vary  in  intensity  according  to  the 
improvement  or  progress  of  the  primary  condition.  A 
certain  nmnber,  though  usually  unassociated  with  any 
other  demonstrable  disorder,  prove  most  resistant  to 
all  forms  of  therapy  and  proceed  from  bad  to  worse. 
I  encountered  such  a  case  in  1913,  the  patient  being 
a  man  of  thirty,  patient  of  Dr.  Richard  Bell  of  Staun- 
ton, Va.,  previously  well,  who  first  suffered  with  nose 
bleeds,  then  with  subcutaneous  hemorrhages  all  over 
his  body,  bleeding  from  his  gums,  and  finally  with  in- 
testinal hemorrhages  of  an  exsanguinating  variety. 
Horse  serum,  calcium,  styptics  of  all  varieties,  and  all 
other  known  methods  of  controlling  bleeding  were 
resorted  to  without  avail  until  his  condition  became 
so  desperate  that  a  blood  transfusion  was  necessary  to 
save  his  life.  A  more  shocking  sight  I  have  never 
seen  than  that  poor  fellow — drops  of  pale,  thin  blood 
were  oozing  from  his  nose  and  gums  to  such  extent 
that  he  was  able  to  articulate  only  between  expectora- 
tions of  mouthfuls  of  blood,  and  his  entire  skin  was 


FOR  HEMORRHAGIC  DISEASES  217 

peppered  with  pui'plish-blue  spots  of  subcutaneous 
hemorrhages  of  all  shapes  and  sizes.  The  transfusion 
stopped  the  bleeding  immediately ;  even  before  its  con- 
clusion, the  oral  and  nasal  ooze  had  ceased,  and  liis 
condition  progi'essively  improved  to  such  extent  that 
he  was  able  to  leave  his  bed  and  seemed  on  the  road  to 
recovery.    Some  months  later  he  died  in  a  recurrence. 

I  have  knowledge  of  another  stubborn  case,  that  of 
a  young  woman,  who  every  once  in  a  while  has  subcu- 
taneous hemorrhages  scattered  over  her  body  and  very 
frequently  has  abdominal  symptoms  of  a  most  obscure 
character,  which  are  probably  nothing  more  than  in- 
testinal manifestations  of  the  same  condition.  Her 
blood  has  been  most  painstakingly  investigated  by 
Dr.  Howell  and  Dr.  Moss  with  negative  findings.  In 
perfect  health  at  present,  she  nevertheless  has  at  the 
present  writing  a  large  purpuric  spot  just  to  one  side 
of  her  soft  palate  which  made  its  appearance  just  the 
other  day  and  is  a  single  manifestation. 

Many  transfusions  have  been  done  for  the  con- 
dition; Peterson  of  New  York  reports  12  transfu- 
sions in  7  cases,  3  of  which  ceased  to  bleed  and  re- 
covered for  the  time  being,  while  2  died.  The  other 
2  relapsed  within  a  period  of  a  year.  This  is  the 
usual  story. 

I  have  under  my  care  now  a  young  girl  of  nine- 
teen, who  has  a  history  of  bleeding  from  the  uterus 


218  BLOOD  TRANSFUSION 

extending  over  a  period  of  eight  years.  Repeatedly 
exsanguinated,  always  more  or  less  in  trouble,  she  was 
transfused  about  one  year  ago  with  temporary  bene- 
fit. When  the  bleeding  recurred  she  was  treated  with 
radium  by  Drs.  Kelly  and  Burnam,  and  the  uterine 
bleeding  ceased.  A  few  months  ago  intestinal  bleed- 
ing became  the  order  of  the  day,  and  her  condition 
progressed  steadily  downwards  until  she  travelled 
from  her  home  in  St.  Louis  to  Baltimore  with  the 
hope  that  radium  would  again  prove  beneficial.  On 
her  arrival,  however,  she  was  so  anaemic  and  weak- 
ened that  a  hurried  transfusion  was  necessary  to  save 
her  life  in  this  emergency;  but  before  resorting  to 
transfusion  it  was  noticed  that,  in  addition  to  her 
active  intestinal  bleeding,  numerous  large  purpuric 
spots  were  scattered  all  over  her  body.  After  twelve 
transfusions  and  a  cecostomy  for  purposes  of  irriga- 
tion this  patient  was  sent  home  looking  the  picture  of 
health,  all  bleeding  stopped  and  with  a  blood  count 
almost  normal.  The  most  striking  feature  of  the  case 
was  an  almost  total  absence  of  platelets.  Even  when 
the  patient's  blood  approached  the  normal  count  but 
little  increase  was  to  be  noted  in  their  number,  though 
late  reports  from  the  family  physician  tell  of  a  slow 
but  steadily  increasing  platelet  count  as  time  wears  on. 
Further  citation  of  cases,  with  which  the  literature 
abounds,  is  superfluous.  In  purpura  we  are  dealing 
with  a  dangerous  obscure  form  of  bleeding  which 


FOR  HEMORRHAGIC  DISEASES  219 

yields  to  no  form  of  therapy  so  far  as  a  cure  is  con- 
cerned, but  which  occasionally  recovers  spontaneously. 
Most  cases  are  mild,  but  many  are  desperate  in  the 
extreme;  even  so,  temporary  recoveries  and  long  re- 
missions may  be  expected  in  certain  of  the  worst. 
Subcutaneous  injections  of  serum  arrest  the  bleeding 
in  some  cases,  intramuscular  injections  of  whole  blood 
stop  it  in  others,  blood  transfusions  apparently  arrest 
it  in  a  great  many  more.  Nothing  will  effect  a  per- 
manent cure  so  far  as  is  known. 

Jaundice. — Bleeding  in  icteric  conditions  is  quite 
common  and  always  dangerous,  yet  there  is  great  con- 
fusion regarding  the  true  nature  of  the  phenomenon. 
The  cause  of  this  uncertainty  is  probably  due  to  the 
fact  that,  although  the  type  of  bleeding  is  the  same 
in  all  forms — being  an  intractable  ooze  from  all  mu- 
cous membranes — the  blood  condition  differs  accord- 
ing as  the  jaundice  is  of  the  obstructive  type  or  of  the 
non-obstructive  type.  In  the  first  variety  there  is  no 
disease  of  the  liver,  while  in  the  second  there  is,  al- 
though it  is  well  to  remember  that  considerable  diffi- 
culty arises  from  a  clinical  inability  to  determine 
which  cases  will  bleed  and  which  will  not.  It  might 
be  thought,  a  priori,  that  the  deeper  the  jaundice  the 
more  likelihood  of  bleeding  following  operation;  this 
may  be  true  to  a  certain  degree,  but  it  cannot  be  taken 
as  a  guiding  rule.  Many  of  the  most  deeply  jaun- 
diced patients  come  through  their  illness  without  a 


220  BLOOD  TRANSFUSION 

sign  of  bleeding  while  others  far  less  jaundiced  come 
to  grief. 

In  many  clinics  the  custom  has  arisen,  as  a  con- 
sequence, of  giving  all  jaundiced  patients  15  grains 
or  more  of  calcium  lactate  as  a  prophylactic  three 
times  a  day  for  several  days  prior  to  and  following 
operation,  but  opinions  diiFer  as  to  the  efficacy  of  the 
treatment  in  preventing  hemorrhage.  The  trouble  is 
that  the  prophylaxis  has  not  been  carried  out  rigidly 
enough  to  really  tell  whether  it  does  or  does  not  help. 
Prevention  is  most  urgent,  however,  since  once  the 
bleeding  has  started  it  is  always  to  be  feared.  Cal- 
cium lactate  practically  never  stops  it,  and  the  various 
sera  are  of  little  more  service,  although  isolated  cases 
are  to  be  found  in  the  literature  where  a  favorable 
outcome  did  follow  their  injection.  Of  the  three — 
rabbit,  horse  and  human  serum — the  human  variety  is 
to  be  preferred,  but  transfusion  of  whole  blood  seems 
to  be  of  more  service  than  any  one  or  all  three  put 
together. 

It  should  be  noted,  though,  that  the  two  conditions 
may  be  associated.  Where  the  jaundice  is  purely  of 
the  obstructive  type,  the  delay  in  blood  coagulation  has 
been  shown  to  be  due  to  a  lack  of  available  calcium  in 
the  blood  caused  probably  by  an  imusual  binding  of 
the  calcium  normally  present  by  the  bile  pigments 
(Whipple)  which  thus  renders  it  useless  for  coagula- 


FOR  HEMORRHAGIC  DISEASES  2«1 

tion  purposes.  To  meet  this  condition  it  has  been  found 
possible  to  administer  calcium  by  mouth,  although  its 
absorption  from  the  intestinal  tract  is  so  slow  that  it 
must  be  administered  over  a  period  of  several  days 
before  any  marked  effect  on  the  coagulation  tissue  is 
seen.  Calcium  lactate  is  usually  employed  in  100- 
grain  doses  a  day.  Intravenous  injection  is  probably 
practicable  but  has  not  been  extensively  used,  chiefly 
on  account  of  the  insolubility  of  the  drug. 

In  the  bleeding  associated  with  liver  changes,  there 
is  rather  conclusive  evidence  to  show  that  the  pro- 
thrombin-antithrombin  ^  balance,  always  of  necessity  a 
most  delicate  one,  has  been  upset  by  the  excessive 
production  of  antithrombin  by  the  liver.  As  a  con- 
sequence the  entire  mechanism  of  blood  coagulation 
is  thrown  out  of  gear  with  the  resultant  well-known 
intractable  fatal  hemorrhages.  And  since  the  fault 
here  has  nothing  to  do  with  calcium  of  the  blood,  it  is 
evident  that  calcium  administration  is  useless,  a  more 
logical  procedure  being  the  administration  of  some- 
thing containing  sufficient  prothrombin  to  bind  the 
excessive  antithrombin  and  thus  bring  about  the  nor- 
mal conditions  necessary  for  blood  coagulation.  The 
blood  of  a  normal  individual,  of  course,  contains  the 
desired  element,  and  it  has  been  found  that  transfusion 
of  fresh  whole  blood  brings  about  the  equilibrium 

'  See  Howell's  theory  of  coagulation,  Chapter  I. 


222  BLOOD  TRANSFUSION 

that  results  in  coagulation  and  cessation  of  bleeding, 
although  it  obviously  can  have  no  effect  on  the  under- 
lying condition  of  the  liver.  So  that  while  trans- 
fusion is  of  definite  service  in  the  non-obstructive 
icteric  conditions  it  must  be  clearly  understood  that 
nothing  of  a  permanent  nature  can  be  expected  unless 
the  hepatic  condition  can  be  rectified. 

In  the  obstructive  type  of  jaundice,  even  trans- 
fusion fails  to  stop  the  bleeding  in  all  cases  and  in 
numerous  instances  the  hemorrhage  has  continued  to 
a  fatal  ending.  It  is  only  fair  to  say,  however,  that 
most  of  the  fatal  cases  have  been  pretty  far  advanced 
when  blood  was  transfused,  this  procedure  being  held 
as  a  last  resort  in  these  patients  for  whom  calcium  is 
usually  started  as  soon  as  the  slightest  bleeding  takes 
place ;  if  it  continues  more  calcium  is  given,  and  if  this 
does  not  stop  it  the  aid  of  serum  is  invoked,  whereas 
early  transfusion  would  probably  save  almost  ever\'  one 
of  them. 

In  concluding  this  chapter  it  may  be  said  that  any 
of  the  hemorrhagic  group  of  diseases  is  to  be  feared 
at  all  times,  because  of  inherent  possibilities  for  dan- 
ger. Based  upon  an  obscurely  deranged  coagulation 
mechanism  that  is  different  in  each  unit  of  the  group, 
diagnosis,  as  a  rule,  is  not  specially  difficult  but  therapy 
is  rather  unsatisfactory,  chiefly,  perhaps,  because  of 
the  obscurity  of  etiology.    The  type  known  as  melaena 


FOR  HEMORRHAGIC  DISEASES  223 

neonatorum  is  the  only  one  which  can  apparently  be 
cm-ed  by  anything  that  will  stop  the  bleeding,  of  which 
agents  transfusion  of  blood  is  by  all  means  the  surest. 
In  the  remaining  types  the  basic  condition  is  appar- 
ently unchanged  by  any  form  of  therapy,  but  in  all 
of  them  the  bleeding  can  usually  be  stopped,  either 
by  sei-um  injections  or  preferably  by  blood  transfu- 
sion, by  which  means  remissions  of  greater  or  lesser 
duration  may  be  secured.  These  alleviations  are  most 
desirable  not  only  because  they  prolong  life,  but 
because  the  conditions,  themselves  of  either  hereditary 
or  spontaneous  origin,  occasionally  vanish  in  a  wholly 
unaccountable  manner. 

REFERENCES 

Cecil,  H.  L. :  "  The  Use  of  Kephalin  to  Hasten  Coagulation 
and  Haemostasis  after  Surgical  Operations."  /.  A.  M.  A., 
Feb.  24,  1917,  vol.  Ixviii. 

Duke,  W.  W. :  "  The  Pathogenesis  of  Purpura  Hemorrhagica 
with  Especial  Reference  to  the  Part  Played  by  Blood 
Platelets."  Arch.  Int.  Med.,  November,  1912,  p.  445. 

Emsheimer,  H.  W. :  "Intramuscular  Injections  of  Whole 
Blood  in  the  Treatment  of  Purpura  Hemorrhagica." 
J.  A.  M.  A.,  January  1,  1916,  vol.  Ixvi,  No.  1. 

Hahn,  Milton :  "  Haemophilia  Treated  by  Transfusion."  Med. 
Record,  October  8,  1910. 

Helmholtz,  H.  F. :  "  The  Longitudinal  Sinus  as  the  Place 
of  Preference  in  Infancy  for  Intravenous  Aspirations 
and  Injections;  including  Transfusion."  Am.  Journ. 
Dis.  Child.,  September,  1915,  p.  194. 


««4  BLOOD  TRANSFUSION 

Hess,  Alfred  F. :  "  The  Calcium  Factor  in  Haemophilia." 
Bulletin  of  the  Johns  Hopkins  Hospital,  November, 
1916,  vol.  xxvi. 

Hess,  Alfred  F. :  "A  Further  Report  on  Thromboplastin 
Solution  as  a  Haemostatic."  J.  A.  M.  A.y  December  9, 
1916,  vol.  Ixvii. 

Hess,  Alfred  F. :  "  Blood  and  Blood-vessels  in  Haemophilia 
and  other  Hemorrhagic  Diseases."  Archives  of  Int. 
Med.,  February,  1916. 

Howell,  W.  H. :  "  Condition  of  Blood  in  Haeanophilia,  Throm- 
bosis and  Purpura."  Arch,  of  Int.  Med.,  January,  1914. 

Lambert,  S.  W. :  "  Melasna  Neonatorum  with  Report  of  a 
Case  Cured  by  Transfusion."  Med.  Rec,  N.  Y.,  May  30, 
1908. 

Lee,  Roger  I.,  and  Vincent,  Beth. :  "The  Relation  of  Calcium 
to  the  Delayed  Coagulation  of  the  Blood  in  Obstructive 
Jaundice."  Archives  of  Internal  Medicine,  July,  1915, 
vol.  xvi,  pp.  69-66. 

Tvcspanasse,  V.  D. :  "  The  Treatment  of  Hemorrhagic  Dis- 
ease of  the  New-Bom  by  Direct  Transfusion  of  Blood. 
With  a  Clinical  Report  of  Fourteen  Personal  Cases." 
J.  A.  M.  A.,  June  13, 1914. 

Moss,  W.  L.,  and  Gelien,  J. :  "  Serum  Treatment  of  Hemor- 
rhagic Diseases."  Special  Tuberculosis  Nu/mher  of  Johns 
Hopkins  Bulletin,  vol.  xxii.  No.  246,  July,  1911. 

Ottenberg,  Reuben  and  Schwarz,  Herman :  "The  Hemorrhagic 
Disease  of  the  Newborn."  Am.  Journal  of  Medical  Sci- 
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Peck,  Charles  H. :  "  Splenectomy  for  Haemolytic  Jaundice." 
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FOR  HEMORRHAGIC  DISEASES  225 

Peterson,  E.  W. :  "  Purpura  Hemorrhagica  Treated  by  Blood 
Transfusion."    Post-Graduate,  N.  Y.,  1914,  xxix,  499. 

Peterson,  E.  W. :  "  Results  from  Blood  Transfusion  in  the 
Treatment  of  Severe  Posthemorrhagic  Anaemia  and  the 
Hemorrhagic  Diseases."  J.  A.  M.  A.,  April  22,  1916. 

Sahli,  H. :  "  Ueber  das  Wesen  der  Hasmophilie."  Ztschr.  f. 
kin.  Med.,  Bd.  56,  1905. 

Schlenker,  Lawrence :  "  Purpura  Hemorrhagica  Treated  vrith 
Normal  Horse  Serum."  J.  A.  M.  A.,  April  1,  1916. 

Schloss,  C  M.,  and  Comminskey,  L.  J.  J. :  "  Spontaneous 
Hemorrhage  in  the  New-Born."  Am.  Journ.  Dis.  ChUd.y 
April,  1911,  p.  276. 

Unger,  L. :  "  Melaea  Neontorumw"  Wiener  Klin.  Woch.,  Sep- 
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Vincent,  Beth:  "  The  Treatment  of  Hemorrhagic  Disease  of 
the  Newborn."  Archives  of  Pediatrics,  December,  1912. 

Vincent,  Beth :  "  Blood  Transfusion  for  Hemorrhagic  Dis- 
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Welch,  J.  E. :  "  Normal  Human  Blood  Serum  as  a  Curative 
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Whipple,  G.  H. :  "  II.  Hemorrhagic  Disease.  Antithrombin 
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mental Biology  and  Medicine,  1914,  xi,  pp.  60-63. 


15 


CHAPTER  XII 

LEUKAEMIA.     SPLENIC  ANEMIA   (BANTI'S  DIS- 
EASE). CERTAIN  TOXEMIAS 

Feom  the  standpoint  of  blood  transfusion,  the 
leuksemias  are  most  discouraging,  chiefly  because  many 
cases  exhibit  such  a  pronounced  change  for  the  better 
immediately  following  the  blood  introduction — only 
to  be  followed  by  a  reversion  to  the  pre-transfusion 
state  in  an  equally  short  period.  In  other  conditions, 
if  any  improvement  occurs  at  all,  it  is  customary  for 
it  to  last  at  least  a  reasonable  period — ^the  remissions 
seen  in  pernicious  anaemia  are  an  example — but  the 
basic  cause  of  leukaemia  is  evidently  an  agent  of  such 
markedly  different  character  that  any  inhibition  of 
its  activities  that  may  be  caused  by  blood  transfusion 
is  only  a  temporary  phase  in  a  steadily  progi-essing 
disease  that  always  ends  fatally. 

A  case  in  point  is  that  of  a  little  boy  twenty-one 
months  old,  the  patient  of  Dr.  John  Ruhrah,  who 
became  ill  in  November  of  1914  and  on  examination 
Was  found  to  be  suffering  from  acute  lymphatic  leuke- 
mia of  such  grave  degree  that  his  course  was  one  of 
rapid  progress  down  hill,  in  spite  of  all  supportive 
treatment.  An  indirect  transfusion  of  90  c.c.  of  blood 
was  followed  by  a  prompt  drop  in  temperature,  a 
definite  fall  in  his  white  cell  count  with  a  change  for 

226 


LEUKEMIA  AND  SPLENIC  ANAEMIA  227 

the  better  in  the  differential  count,  and,  best  of  all, 
a  rise  in  his  red  cells  and  haemoglobin.  The  child's 
physical  condition  improved  correspondingly,  he  be- 
gan to  relish  his  food,  he  lost  his  waxy  look,  was  able 
to  be  up  and  about,  and  had  even  been  taken  out  for  a 
walk  by  his  nurse  when  he  suddenly  relapsed — only 
thi'ee  or  four  weeks  after  the  beginning  of  his  re- 
mission. From  that  time  on  his  downward  course  was 
even  more  rapid,  and  a  second  transfusion  was  utterly 
unavailing.  He  died  just  seven  weeks  after  the  first 
introduction  of  blood. 

A  case  almost  identical  with  this  occurred  in  a  man 
of  forty-eight  years,  a  patient  of  Dr.  W.  T.  Willey, 
who  had  undergone  without  improvement  a  course  of 
X-ray  treatments  prior  to  my  seeing  him.  His  count 
before  transfusion  was  red  blood-cells,  1,360,000 ;  white' 
blood-cells,  356,000  (98  per  cent,  lymphocytes) ;  hae- 
moglobin, 20  per  cent.  'I'wo  and  a  half  weeks  later, 
after  his  second  transfusion,  his  count  was  red  blood- 
cells,  1,840,000;  white  blood-cells,  108,000;  haemoglo- 
bin, 32  per  cent.,  snowing  a  marked  diminution  in  the 
number  of  his  white  cells,  although  differentially  they 
were  still  largely  composed  of  lymphocytes.  His 
physical  condition  was  very  much  better  *  during  this 

*  Blood  transfusion  has  been  used  in  leukaemia  not  with 
any  idea  of  effecting  a  cure  but  rather  in  the  hope  that  the 
condition  might  be  influenced  to  take  on  a  chronic  form,  with 
a  resultant  prolongation  of  life. 


BLOOD  TRANSFUSION 

time  and  it  began  to  look  as  if  some  real  benefit  might 
come  about,  when  an  unaccountable  enlargement  of 
the  glands  in  the  left  side  of  the  neck  became  apparent. 
From  that  time  on,  the  patient  rapidly  lost  ground. 
His  white  cells  became  as  numerous  as  ever,  he  was 
unable  to  build  any  red  cells,  his  haemoglobin  fell, 
and  he  began  to  have  slight  bleedings  from  the  gums, 
and  irritating  ulcers  of  the  tongue.  A  third  trans- 
fusion was  performed  but  was  unavailing,  the  patient 
dying  of  a  terminal  pneumonia  a  short  time  later. 

I  have  had  a  few  other  cases  of  this  kind ;  they  have 
all  gone  the  same  way,  and  others  have  had  similar 
corroborative  experiences.  It  may  therefore  be  con- 
cluded that  transfusion  can  offer  little  or  no  hope  in 
the  condition.  Just  why  the  introduction  of  fresh 
blood  causes  even  a  temporaiy  halt  in  the  disease  I  am 
at  a  loss  to  say,  and  how  it  destroys  the  white  cells  is 
equally  obscure.  Perhaps  there  is  no  destruction,  for 
it  is  conceivable  that  the  lowered  white  cell  count  may 
be  due  to  blood  dilution  consequent  upon  increased 
blood  bulk  or  a  diminished  output  of  white  cells. 
Whatever  the  cause,  the  new  blood  is  of  little  sustain- 
ing power  since  the  old  regime  soon  recommences, 
apparently  possessed  of  even  increased  vigor. 

Splenic  ancemia  or,  as  it  is  called  in  its  later  stages, 
BantVs  disease,  is  apparently  cured  by  removal  of  the 
spleen,  and  is  concerned  with  transfusion  only  when  the 


LEUKiEMIA  AND  SPLENIC  ANEMIA  229 

anaemia  becomes  so  pronoimced  that  new  blood  is  de- 
sired in  order  to  decrease  the  operative  risk.  Trans- 
fusion alone  will  favorably  influence  the  ansemia,  but 
since  splenectomy  has  proved  to  be  of  such  undoubted 
value,  simple  transfusion  is  not  to  be  considered  as 
adequate  treatment. 

A  most  instructive  case  in  point  was  that  of  a 
little  boy  of  eight,  a  patient  of  Dr.  W.  S.  Thayer, 
who  had  had  splenic  ansemia  for  several  years  until 
finally  no  hope  remained  for  him  but  removal  of  the 
spleen.  His  blood  picture  was  so  low  that  a  pre- 
liminary transfusion  was  done  the  day  before  opera- 
tion, but  a  few  hours  later  the  boy  vomited  practically 
every  drop  of  blood  given  him,  probably  from  a  rup- 
tured oesophageal  or  gastric  varix.  Next  morning  he 
was  transfused  again,  and  during  the  actual  course  of 
the  blood  transfusion  his  spleen  was  removed  by  Dr. 
J.  M.  T.  Finne}\  A  gradual  but  quite  satisfactory 
recovery  ensued,  and  he  left  the  hospital  in  good  condi- 
tion, only  to  die  several  months  later  from  another 
gastric  hemorrhage. 

In  certain  forms  of  toxaemia  and  certain  poisons, 
blood  transfusion  has  seemed  to  be  of  value,  but  the 
number  of  cases  reported  is  so  limited,  that  little  of 
an  authentic  nature  can  really  be  said  and  I  merely 
mention  the  possible  agency  of  transfusion  in  these 
conditions  for  the  sake  of  completeness. 


290  BLOOD  TRANSFUSION 

A  few  transfusions  have  been  carried  out  in 
eclampsia  and  the  toxaemia  of  pregnancy.  In  the 
latter  condition,  Keator  reports  a  successful  case,  and 
one  of  my  own  seemed  about  to  have  a  successful  out- 
come when  an  unexpected  heart  collapse  thirty-six 
hours  after  transfusion  ended  matters.  In  neither 
eclampsia  nor  toxsemia  of  pregnancy  would  I  think  of 
advocating  blood  transfusion  as  a  cure,  since  in  general 
the  proper  obstetrical  measures  bring  about  relief,  but 
it  seems  worthy  of  a  more  extended  trial  in  those  ful- 
minating cases  where  obstetrical  resources  have  proved 
unavailing  and  a  fatal  ending  appears  imminent.  Pre- 
liminary bleeding  probably  should  be  carried  out  prior 
to  the  introduction  of  the  fresh  blood  in  order  to 
eliminate  as  much  toxic  matter  as  possible. 

Of  the  poisons,  illuminating  gas  has  been  shown  to 
yield  best  to  the  introduction  of  new  blood,  but  the 
pulmotor  as  used  by  the  various  gas  companies  seems 
to  give  as  good  results  as  can  be  expected  in  the  ma- 
jority of  cases.  I  have  never  done  a  transfusion  for 
the  relief  of  this  condition,  and  few  are  found  in  the 
literature,  although  it  has  been  the  subject  of  a  con- 
siderable amount  of  experimental  work. 

A  most  brilliant  result  followed  transfusion  in  a 
case  of  benzol  poisoning  treated  in  the  Johns  Hopkins 
Hospital  in  1914.  Repeated  transfusions  were  car- 
ried  out   by   Dr.    R.    D.    McClure,    who   reported 


LEUKAEMIA  AND  SPLENIC  ANEMIA  231 

the  case  before  the  1916  meeting  of  the  American 
Medical  Association.  So  far  as  I  am  aware,  it  is 
the  only  case  of  the  kind  on  record,  due  probably  to  the 
fact  that  benzol  poisoning  is  so  rarely  encomitered. 

REFERENCES 
Bunting,  C.  H.,  and  Yates,  J.  L. :  "  Bacteriological  Studies 

in  Chronic  Leukaemia  and  in  Pseudoleulcaemia."  Bulletin 

of  the  Johns  Hopkins  Hospital,  November,  1915,  vol. 

xxvi. 
Burmeister,  W.  H. :  "  Resuscitation  by  Means  of  Preserved 

Living  Erythrocytes  in  Experimental  Illuminating  Gas 

Asphyxia."  J.  A.  M.  A.,  January  15,  1916. 
Ely,  A.  H.,  and  Lindeman,  Edward :  "  Acidosis  Complicating 

Pregnancy ;  Report  of  Case  Cured  by  Transfusion."  Am. 

Journal  of  Ohstet.  and  Dis.  of  Women  and  ChUdren, 

July,  1916,  Ixxiv,  No.  1. 
Crettler,  Alexander  O.,  and  Lindeman,  Edward :  "  A  New 

Method  of  Acidosis  Therapy;  Blood  Transfusion  from 

an  Alkalinized  Donor  with  Report  of  Case."    J.  A.M.  A., 

vol.  Ixviii,  No.  8,  February  24,  1917. 
Keator,  H.  M. :  "  Transfusion  in  Case  of  Toxaemia  of  Early 

Pregnancy  with  unusual  Hemorrhagic  Manifestations." 

American  Journal  Ohstet.   and  Diseases   of  Children, 

June,  Ixv,  No.  414,  pp.  937-1131. 
Packard,  Maurice,  and  Ottenberg,  Reuben :  "  The  Leuko- 

toxic  Factor  in  Lymphatic  Leukaemia."     /.  A.  M.  A.t 

March  31,  1917,  vol.  Ixviii. 
Mayo,  Wm.  J. :  "  The  Spleen ;  Its  Association  with  the  Liver 

and  its  Relation  to  Certain  Conditions  of  the  Blood." 

J.  A.  M.  A.,  March  4, 1916. 


ftSSt  BLOOD  TRANSFUSION 

McClure,  Roy  D. :  "  Pernicious  Anasmia  Treated  by  Splenec- 
tomy and  Systematic,  Often-Repeated  Transfusion  of 
Blood.  Transfusion  in  Benzol  Poisoning."  J,  A.  M.  A., 
September  9,  vol.  Ixvii,  pp.  793,  796. 

Pool,  Eugene  H. :  "  Transfusion  and  Splenectomy  for  Von 
Jaksch's  Anaemia  in  an  Infant."  Annals  of  Surgery, 
March,  1915.     In  Transactions  of  N.  Y.  Surg.  Soc. 

Rodman,  J.  S.,  and  Willard,  F.  P. :  "  Splenic  Anaemia  with 
Special  Reference  to  Etiology  and  Surgical  Treatment." 
Annals  of  Surgery,  November,  1913. 

Stillman,  Ralph  G. :  "A  Study  of  Von  Jaksch's  Anaemia." 
American  Journal  of  the  Medical  Sciences,  vol.  cliii, 
No.  2,  February,  1917,  p.  218. 


APPENDIX 

CONTAINING  HJEMOLYTIC  AND  AGGLUTINATION 
TESTS  THAT  ARE  TO  BE  CARRIED  OUT  PRE- 
LIMINARY TO  EVERY  BLOOD  TRANSFUSION 
EXCEPT  THOSE  OF  THE  MOST  URGENT 
CHARACTER.  THE  TESTS  GIVEN  ARE  AS 
FOLLOWS:  (1)  MOSS'  METHOD  OF  GROUP 
TESTING;  (2)  BREM'S  SIMPLIFICATION  OF 
MOSS'  GROUP  METHOD;  (3)  SIMON'S  METHOD 
OF  TESTING  OUT  DONORS  DIRECTLY 
AGAINST  THE  RECIPIENTS;  (4)  SYDEN- 
STRICKER'S  METHOD  OF  TESTING  OUT 
DONORS  DIRECTLY  AGAINST  THE  RE- 
CIPIENT. 

MOSS^  METHOD  OF  GKOUPING  BLOODS  FOR  TRANSFUSION. 

According  to  Moss,i  whose  article  on  Isoagglu- 
tinins  and  Isohemolysins,  written  in  1910,  still  remains 
an  undimmed  landmark,  all  individuals  can  be  divided 
into  four  groups  as  regards  their  blood  according  to 
the  ability  of  their  serum  to  agglutinate  the  corpuscles 
of  other  individuals,  and  according  to  the  ability  of 
their  corpuscles  to  be  agglutinated  by  the  serum  of 
other  individuals. 

1  W.  L.  Moss,  "  Studies  on  Isoagglutinins  and  Isohemoly- 
sins."   Bulletin  of  the  Johns  Hopkins  Hospital,  vol.  xxi,  No. 

228,  March,  1910,  pp.  63-70. 

233 


284  APPENDIX 

These  gi-oups  which  were  based  originally  on  1600 
tests,  have  been  borne  out  by  thousands  of  subsequent 
tests  by  numbers  of  observers  and  are  as  follows: 

Group  I  (10  per  cent.)  :  Sera  agglutinate  no  corpuscles. 
Corpuscles  agglutinated  by  sera  of  Groups  II,  III  and  IV. 

Group  II  (40  per  cent.) :  Sera  agglutinate  corpuscles  of 
Groups  I  and  III.  Corpuscles  agglutinated  by  sera  of  Groups 
III  and  IV. 

Group  III  (7  per  cent.)  :  Sera  agglutinate  corpuscles  of 
Groups  I  and  II.  Corpuscles  agglutinated  by  sera  of  Groups 
II,  IV. 

Group  IV  (43  per  cent.) :  Sera  agglutinate  corpuscles 
of  Groups  I,  II  and  IV.  Corpuscles  agglutinated  by  no 
serum. 

The  details  of  the  test  are  as  follows : 

"  The  technic  employed  in  all  of  the  tests  here  re- 
ported was  carried  out  with  surgical  asepsis,  and  great 
care  was  taken  that  the  syringe,  pipettes,  test-tubes, 
and  all  glassware  used  were  not  only  sterile  but  very 
clean.  Blood  is  taken  from  a  vein  at  the  elbow.  For 
this  purpose  the  skin  over  the  vein  is  rendered  aseptic 
and  about  20  c.c.  of  blood  is  withdrawn  by  means  of 
a  syringe  which  previously  has  been  boiled  and  then 
washed  out  with  a  solution  containing  1.5  per  cent, 
sodium  citrate  and  0.85  sodium  chloride;  this  riemoves 
any  water  which  remains  in  the  syringe  after  boiling 
and  which  might  cause  slight  laking  of  the  blood.  Two 
sterile  centrifuge  tubes  are  ready  to  receive  the  blood 


APPENDIX  235 

as  soon  as  it  is  withdrawn,  one  being  empty  and  the 
other  containing  10  or  12  c.c.  of  1.5  per  cent,  sodium 
citrate  in  0.85  per  cent,  sodimn  chlordde  solution.  Into 
the  tube  containing  the  sodium  citrate,  3  c.c.  of  blood 
is  introduced  for  corpuscles,  and  the  remaining  blood 
is  put  into  the  other  tube  for  serum.  The  corpuscles 
are  further  prepared  by  centrifugalizing  them  out  of 
the  sodium  citrate  solution,  pipetting  off  the  super- 
natant fluid  and  washing  them  twice  with  0.85  per 
cent,  sodium  chloride  solution  to  free  the  cells  from 
serum.  After  the  last  centrifugalization,  which  is  con- 
tinued until  the  cells  are  thoroughly  sedimented,  the 
supernatant  fluid  is  pipetted  off  and  0.5  c.c.  of  the 
corpuscles  is  transferred  to  9.5  c.c.  of  0.85  per  cent, 
sodium  chloride  solution,  thus  making  a  5  per  cent, 
suspension. 

"  The  tube  containing  the  blood  of  the  serum  is 
allowed  to  clot  and  after  about  half  an  hour  the  clot 
is  carefully  separated  from  the  sides  of  the  tube  with 
a  sterile  platinum  needle,  after  which  the  serum  is 
easily  obtained  by  a  few  minutes'  centrifugalization. 
The  clear  serum  is  then  pipetted  off  from  the  clot  and 
transferred  to  another  tube.  Serum  and  corpuscles 
are  similarly  obtained  from  a  number  of  individuals. 

"  The  further  procedure  consists  in  combining 
equal  quantities  (usually  0.25  or  0.5  c.c.)  of  serum 
and  suspension  of  the  corpuscles  so  that  the  action  of 


236  APPENDIX 

each  serum  is  tested  on  the  corpuscles  of  every  mem- 
ber of  the  series  separately.  These  mixtures  having 
been  made,  the  tubes  are  shaken  to  distribute  the  cor- 
puscles evenly  through  the  serum,  and  are  then 
allowed  to  stand  in  the  thermostat  at  37.5°  C.  for  two 
hours,  after  which  they  are  placed  in  the  icechest  over 
night.  Readings  are  made  at  the  end  of  the  two  hours 
in  the  thermostat  and  after  the  tubes  have  stood  over 
night  in  the  icechest.  Agglutination  and  hsemolysis 
are  easily  determined  by  the  naked  eye,  and  the  results 
of  the  reading  at  the  end  of  two  hours  in  the  ther- 
mostat and  after  having  stood  over  night  in  the  ice- 
chest differ,  if  at  all,  only  slightly  in  amoimt. 

"  Before  examining  the  results  obtained,  it  may  be 
stated  that  no  constant  differences  were  found  be- 
tween the  agglutinating  or  haemolysing  abilities  of  sera 
in  health  and  in  disease.  The  serum  of  a  healthy  indi- 
vidual might  agglutinate  or  hiemolyse  the  corpuscles 
of  some  healthy  individuals,  but  fail  to  agglutinate  or 
hffimolyse  those  of  other  healthy  individuals  and  the 
same  variations  were  noted  in  its  action  on  the  cor- 
puscles of  patients  suffering  from  a  variety  of  dis- 
eases. The  same  relations  were  found  to  exist  be- 
tween the  serum  in  disease  and  the  corpuscles  of  dis- 
eased and  healthy  individuals.    .     .     . 

"  In  regard  to  the  relationship  existing  between 
isoagglutinins  and  isohsemolysins,  I  may  say  that  ag- 


APPENDIX  237 

glutination  frequently  occurs  independently  of  hsemo- 
lysis,  but  that  the  inverse  relation  occurs,  i.e.,  haemo- 
lysis without  the  simultaneous  or  preceding  occur- 
rence of  agglutination  seems  less  likely.  In  my  first 
experiments  hcemolysis  without  agglutination  was  fre- 
quently recorded,  but  closer  attention  to  this  point  in 
subsequent  experiments  led  me  to  doubt  the  correct- 
ness of  earlier  observations. 

"Agglutination  is  a  phenomenon  which  concerns 
the  corpuscle  as  a  whole,  while  haemolysis  is  a  phe- 
nomenon which  destroys  the  integrity  of  the  corpuscle, 
and  it  is  possible  that  agglutination  cannot  persist 
among  corpuscles  which  have  been  damaged  by  the 
action  of  haemolysins.  As  a  rule,  however,  agglutina- 
tion proceeds  more  rapidly  than  does  haemolysis  and 
by  observing  the  action  of  a  serum,  which  contains 
both  agglutinin  and  haemolysin,  on  susceptible  cor- 
puscles, one  frequently  sees  agglutination  set  in  which 
is  subsequently  broken  up  as  haemolysis  takes  place; 
so  that  if  the  observations  are  not  made  until  the  lapse 
of  two  hours,  in  a  case  where  the  haemolysin  is  not 
quite  sufficient  to  dissolve  completely  all  of  the  cor- 
puscles present,  we  may  get  the  appearance  of  haemo- 
lysis having  taken  place  without  agglutination." 

Certain  of  Moss*  conclusions  that  might  be  helpful 
are  as  follows : 


238  APPENDIX 

"  I.  Isoagglutinins  occur  in  the  senini  of  about 
90  per  cent.,  and  isohaemolysins  in  about  25  per  cent, 
of  adult  human  beings. 

"II.  These  bodies  appear  with  approximately 
the  same  relative  frequency  in  health  and  in  various 
diseases  and  therefore  have  no  diagnostic  significance. 

"  III.  Human  beings  can  be  divided  into  four 
groups  according  to  the  ability  of  their  serum  to  cause 
isoagglutination  and  of  their  corpuscles  to  be  isoag- 
glutinated. 

"  IV.  The  serum  of  members  of  any  one  group 
will  not  agglutinate  or  hsemolyse  the  corpuscles  of 
other  members  of  the  same  group  but  will  agglutinate 
and  may  haemolyse  the  corpuscles  of  members  of  any 
other  group  except  those  of  Group  IV.  This  may 
have  a  practical  application  in  the  transfusion  of  blood 
from  one  individual  to  another. 

"  V.  Isoagglutination  may  occur  independently  of 
isohaemolysis  but  isohsemolysis  is  probably  always  pre- 
ceded or  accompanied  by  isoagglutination." 

brem's  method  of  group  testing 

Moss's  method  of  grouping  bloods  has  been  some- 
what simplified  by  numerous  investigators,  all  such 
short-cuts  having  for  their  basis  one  or  two  known 
bloods.  Probably  the  best  known  is  that  of  Walter  V. 
Brem.^  the  technic  of  which  is  as  follows: 


APPENDIX  239 

"  Let  II  represent  a  known  blood  belonging  to 
Group  2,  and  X  a  blood  the  group  of  which  must  be 
determined.  Five  or  six  drops  of  II  blood  are  col- 
lected in  a  small  clean  dry  test  tube  or  centrifuge 
tube,  and  1  or  2  drops,  according  to  the  size  of  the 
drops,  in  another  tube  containing  1  c.c.  of  1.5  per  cent, 
sodium  citrate  in  0.9  per  cent,  salt  solution,  which 
gives  one  approximately  a  5  per  cent,  suspension  of 
corpuscles.  The  percentage  does  not  have  to  be  exact. 
The  X  blood  is  collected  in  the  same  way  in  two  similar 
tubes.  The  bloods  in  the  dry  tubes  are  allowed  to 
coagulate,  the  coagulum  is  loosened  from  the  side  of 
the  tube  with  a  platinum  wire,  and  the  tubes  centrif  u- 
galized  to  separate  the  serum.  Serum  and  corpuscles 
are  now  ready  for  the  tests.  Platinum  loopfuls  of 
serum  and  corpuscles  are  placed  on  coverslips,  which 
are  inverted  over  an  ordinary  cell  slide  rimmed  with 
petrolatum.  Two  loopfuls  of  serum  are  used  and  one 
of  corpuscle  suspension.  The  slides  are  gently  rolled 
from  side  to  side  to  agitate  the  corpuscles  in  order  to 
bring  them  into  contact  with  each  other.  Agglutina- 
tion, if  it  occurs,  takes  place  at  room  temperature 
within  five  minutes.  It  can  usually  be  detected  with 
the  naked  eye,  showing  as  brick  red  particles,  but 

2  Walter  V.  Brem,  "  Blood  Transfusion  with  Special  Ref- 
erence to  Group  Tests,"  (J.  A.  M.  A.,  July  15,  1916,  vol. 
No.  3,  p.  190.) 


MO  APPENDIX 

should  be  examined,  also,  with  the  low  power  objective 
of  the  microscope.  Rouleaux  formation  of  red  cor- 
puscles must  be  differentiated  from  small  clumps  due 
to  agglutination." 

Illusteations  of  Gboup  Determinations  (the  Figuees 
Refer  to  Loopfuls) 
2  II  serum  -f-   1    a?  corpuscles  =  agglutination 
2    X  serum   -f"   1   H  corpuscles  =  0 

Group  2  serum  agglutinates  the  corpuscles  of 
Group  1  and  3  only.  But  Group  3  serum  agglutinates 
the  corpuscles  of  Group  2,  which  does  not  happen  in 
the  foregoing  test  with  X  sei*mn  and  II  corpuscles. 
The  X  blood  does  not  belong,  therefore,  to  Group  3, 
but  must  belong  to  Group  1. 

2  II  serum   -[-la:  corpuscles  =  agglutination 
%    X  serum   -|-   1   II  corpuscles  =  agglutination 

Each  serum  agglutinates  the  other  coi*puscles,  so 
the  two  bloods  belong  to  the  reciprocal  Groups  2  and 
3,  that  is,  the  X  blood  belongs  to  Group  3. 

2  II  serum  -j-   1    j:  corpuscles  =  0 

2  X  serum  4"  1  II  corpuscles  =  agglutination 
Group  2  serum  does  not  agglutinate  Group  2 
or  Group  4  corpuscles,  while  it  does  agglutinate  the 
corpuscles  of  Groups  1  and  3.  The  X  blood  belongs, 
therefore,  to  Group  2  or  Group  4.  Which  one  is  de- 
teraiined  by  testing  X  serum  against  II  corpuscles, 
which  it  agglutinates.    A  serum  does  not  agglutinate 


APPENDIX  241 

corpuscles  belonging  to  its  own  group,  so  the  X  blood 
does  not  belong  to  Group  2,  but  must  belong  to  Group 
4,  the  serum  of  which  does  agglutinate  Group  2  cor- 
puscles. 

2  II  serum  -{-  1    a:  corpuscles  =  0 

2    X  serum  -|-   1  II  corpuscles  =  0 

The  X  blood  belongs  to  the  same  group  as  the 
blood  used  for  testing.  Group  2. 

According  to  Brem,  this  method  of  determining 
the  group  of  an  unknown  blood  requires  not  more  than 
fifteen  minutes  after  the  bloods  are  obtained,  and 
only  small  quantities  of  blood  such  as  can  be  obtained 
from  a  puncture  of  the  finger  tip,  are  necessary.* 

TEST  FOR  AGGLUTINATION  AND  HEMOLYSIS  AS  CAEEEED 

OUT  BY  DR.  CHARLES  E.  SIMON  OF  THE 

UNIVERSITY  OF  MARYLAND. 

By  many  men  it  is  considered  quite  unnecessary  to 
carry  out  the  group  method  of  testing,  a  more  direct 
means  of  attaining  the  same  end  being  that  of  testing 
all  prospective  donors  directly  against  the  recipient 
imtil  a  suitable  donor  is  secured.  Such  a  test  is  as 
follows : 

^  A  most  excellent  article  on  the  subject  of  Agglutina- 
tion and  Haemolysis  is  that  by  Minot.  It  is  comprehensive, 
gives  numerous  tests,  and  contains  a  carefully  selected  list  of 
references.  See  Minot,  George  R. :  "  Methods  for  Testing 
Donors  for  Transfusion  of  Blood  and  Consideration  of  Fac- 
tors Influencing  Agglutination  and  Haemolysis."  The  Boston 
Medical  and  Surgical  Journal,  May  11, 1916,  p.  667. 


242  APPENDIX 

1.  Preparation  of  Serum  and  Blood-cell  Suspen- 
sions.— A  few  drops  of  blood  from  each  of  the  donors 
and  from  the  recipient  are  collected  in  small  dry  glass 
test  tubes.  A  few  drops  from  each  donor  and  the 
recipient  are  also  placed  in  tubes  containing  about  five 
cubic  centimeters  of  a  1.5  per  cent,  solution  of  sodium 
citrate  in  physiological  salt  solution.  Each  tube  is 
marked  carefully  for  identification  as  soon  as  obtained. 

The  undiluted  specimens  of  blood  are  centrifugal- 
ized,  the  sera  pipetted  off  (each  serum  with  its  indi- 
vidual pipette)  and  transferred  to  correspondingly 
labeled  dry  test  tubes.  The  specimens  collected  in 
citrate  are  centrifugalized,  the  supernatant  fluid  pi- 
petted off  (each  with  its  individual  pipette)  and  dis- 
carded, and  the  cells  remaining  washed  a  couple  of 
times  with  saline  solution.  Very  thin  and  homogene- 
ous normal  saline  suspensions  of  each  specimen  of 
washed  cells  are  finally  prepared. 

2.  Preparation  of  Mixture  of  Donor's  Cells  and 
Recipient's  Serum  and  vice  versa. — A  series  of  glass 
slides  (as  many  slides  as  there  are  prospective  donors) , 
is  prepared  as  follows :  On  one  side  of  each  slide  two 
small  rings  of  vaseline  are  made,  one  toward  either 
end.  The  inside  diameter  of  these  rings  should  be 
about  1  to  1.5  centimeters.  The  slides  are  labeled  so 
as  to  correspond  with  the  identification  mark  of  each 
donor.    Each  slide  thus  has  two  vaseline  "  chambers  " 


APPENDIX  243 

and  represents  one  donor.  The  right  hand  chambers 
are  marked  "  S  "  (sermii)  and  the  left  hand  chambers 
"  C  "  (corpuscles). 

Into  each  "  S  "  chamber  is  placed  a  drop  of  senam 
from  the  corresponding  donor,  while  into  each  "  C  " 
chamber  is  placed  a  drop  of  the  blood  cell  suspension 
from  the  corresponding  donor.  To  all  of  the  "  S  '* 
chambers  is  then  added  a  drop  of  the  washed  cell  sus- 
pension of  the  recipient,  and  to  all  the  "  C  "  chambers 
a  drop  of  the  recipient's  serum.  The  contents  of  each 
chamber  are  thoroughly  mixed.  Each  chamber  is  then 
sealed  b}^  carefully  superimposing  glass  coverslips 
over  the  vaseline  rings.  With  a  little  dexterity  the 
sealing  can  be  effected  so  as  to  spread  out  the  contents 
of  each  chamber  into  a  very  thin  layer  between  the 
slide  and  the  cover  slip.  The  specimens  are  now 
placed  in  the  thermostat  at  37°  C,  and  observed  for 
agglutination  and  hsemolysis  at  the  end  of  one  horn*, 
and  again  after  a  second  hour.  In  cases  of  emer- 
gency, it  may  be  necessary  to  shorten  the  incubation 
period  to  one-half  hour,  but  two  hours'  incubation 
is  advisable. 

In  cases  of  extensive  haemolysis  or  agglutination 
majcroscopic  examination  will  reveal  respectively  a 
transparent  reddish  film  or  a  granular  opacity.  This 
is  occasionally  observed  at  the  preliminaiy  examina- 
tion, more  often  at  the  end  of  the  first  hour  of  incuba- 


844  APPENDIX 

tion,  but  occasionally  only  at  the  final  observation — 
henoe  the  advisability  of  prolonged  incubation. 

For  the  recognition  of  less  extensive  haemolysis  or 
agglutination  the  microscope  is  necessary.  The  prepa- 
rations should  be  examined  with  both  low  and  high 
power  dry  lenses.  Thus  observed,  specimens  exhibit- 
ing no  agglutination  show  the  red  cells  uniformly  dis- 
tributed on  the  floor  of  the  chamber  throughout  the 
entire  area  covered  by  the  film.  Careful  search  for 
cell  "  shadows  "  (the  shell-like  stroma  of  haemolized 
red  blood  cells)  is  then  made.  The  presence  of  any 
appreciable  number  of  these  should  exclude  the  indi- 
vidual in  question  as  a  donor.  When  the  haemolysis 
is  extensive,  scarcely  any  cells  remain  intact. 

Interpretation, — Any  slide,  both  of  whose  cham- 
bers contain  specimens  which  show  neither  agglutina- 
tion nor  haemolysis,  as  thus  described,  represents  blood 
homologous  with  the  recipients.  The  donor  whose 
identification  mark  such  a  slide  bears,  is  a  suitable  one 
from  this  point  of  view. 

TEST  FOE  HEMOLYSIS  AND  AGGLUTINATION   USED   BY 

DR.  V.  P.  SYDENSTRICKER,  OF  THE  JOHNS  HOPKINS 

HOSPITAL. 

Another  method  of  directly  testing  out  donors 
against  a  recipient  is  that  commonly  used  at  the  Johns 
Hopkins  Hospital  at  the  present  time  by  Dr.  V.  P. 
W.  Sydenstricker.    It  is  as  follows: 


APPENDIX  245 

Blood  is  drawn  from  each  donor  and  from  the 
recipient,  either  by  venopunctm*e  or  into  a  Wright 
tube  from  a  prick  in  the  finger  or  ear.  At  least  three 
cubic  centimeters  of  blood  should  be  collected  and 
allowed  to  clot  to  obtain  clear  serum.  Two  drops  of 
blood  are  allowed  to  drip  into  5  c.c.  of  1.25  per  cent, 
sodium  citrate  solution  in  0.8  per  cent,  salt  in  order 
to  obtain  a  suspension  of  corpuscles. 

In  performing  the  tests  covershps  should  be  thor- 
oughly clean  and  entirely  free  from  dust  and  lint. 
Capillary  pipettes  should  be  used  in  making  the  prepa- 
rations. We  have  found  those  drawn  from  4  mm. 
glass  tubing  most  satisfactor5^  Coverslips  and  pi- 
pettes should  never  be  used  more  than  once.  One  drop 
of  donor's  serum  and  one  drop  of  recipient's  corpuscle 
emulsion  are  placed  side  by  side  on  a  coverslip  and 
thoroughly  mixed  by  stirring  with  a  small  stirring  rod 
made  from  the  tip  of  a  capillary  pipette.  The  mixed 
drop  should  be  spread  out  so  that  when  the  coverslip  is 
inverted  the  cells  will  not  settle  to  the  lower  part  of  the 
drop,  the  coverslip  is  then  inverted  over  a  hollow- 
ground  slide  and  sealed  with  oil,  it  should  be  examined 
under  the  microscope  at  this  stage  to  be  sure  that  the 
preparation  is  satisfactory;  the  red  cells  should  be 
evenly  distributed  over  the  field,  touching  but  not 
overlapping  one  another.  The  process  is  now  repeated 
using  recipient's  serum  and  donor's  corpuscles.    Con- 


246  APPENDIX 

trols  should  be  run  on  each  corpuscle  emulsion  using 
salt  solution  instead  of  serum  to  be  sure  that  there  is 
no  clumping  of  the  cells  in  the  emulsion  itself. 

The  hanging  drops  should  be  allowed  to  incubate 
at  37°  C.  for  one  hour  before  haemolysis  or  agglutina- 
tion can  be  excluded.  Many  reactions  would  be 
avoided  if  this  rule  were  strictly  followed.  Several 
instances  in  which  agglutination  and  haemolysis  were 
absent  at  the  end  of  thirty  minutes  have  shown  marked 
agglutination  at  the  end  of  an  hour.  Agglutination 
may  occur  with  great  rapidity,  however,  in  some  cases 
before  the  specimen  can  be  examined.  Agglutination 
is  usually  easy  to  recognize,  the  cells  form  clumps  of 
varying  size  and  soon  lose  their  identity  forming  a  con- 
glomerate mass  in  which  the  cell  outlines  can  be  recog- 
nized only  with  difficulty.  Haemolysis  is  often  more 
difficult  to  recognize  in  microscopic  preparations  but 
since  it  is  uniformly  preceded  by  agglutination  it 
should  not  be  missed.  When  it  does  occur  agglutina- 
tion is  evident  but  the  preparation  seems  to  have 
markedly  fewer  cells  in  it  than  when  first  set  up,  on 
careful  focussing  the  "  shadows  "  of  the  haemolyzed 
cells  can  be  made  out  and  if  the  slide  be  held  over  a 
white  surface  the  drop  has  a  distinct  yellow  tinge 
which  is  not  present  when  haemolysis  has  not  taken 
place. 

When  material  is  not  available  for  performing  the 


APPENDIX  247 

microscopic  tests  the  gross  method  may  be  used.  The 
blood  should  be  collected  in  the  same  way  except  that 
it  is  preferable  to  wash  the  cells  used  in  the  emulsion 
by  centrifugalization  to  remove  the  citrate  present. 
The  centrifuged  cells  are  then  emulsified  in  normal 
salt  solution,  the  sera  and  corpuscle  emulsion  are 
mixed  in  ^  c.c.  amounts  in  small  test  tubes  and  incu- 
bated for  an  hour.  When  agglutination  occurs  there 
is  a  "  brick-dust "  sediment  in  the  tubes,  the  super- 
natant fluid  being  colorless ;  haemolysis  is  present  when 
there  is  the  slightest  red  stain  in  the  supernatant  fluid. 


INDEX 


Accidental  gastric  ulcer,  147 

hemorrhage,  151 
Acute  hemorrhage,  155 

measures      to      be 
adopted   in,    166 
transfusion  in,  147 
Agglutination,  53 

phenomenon  of,  69 
sudden  death  from,  69 
test  for,  241,  244 
Air-hunger,  153 

as  a  symptom  in  hemor- 
rhage, 19 
Anaemia,  14 

combating  profound,  49 
danger  signals  in,  3 
increasing  pallor  in,  3 
red  blood-cells  in,  184 
shortness  of  breath  in,  3 
weakness  in,  3 
idiopathic,  182 
pernicious,  14 

Krumbhaar's     con- 
clusions   regard- 
ing,  197 
remissions  in,  185 
size    of    spleen    in, 

192 
transfusion  in,  186 
primary  pernicious,  181 
splenic,  226,  228 


Anaemias,  1,  3 

secondary,  171 
Anaemic  and  debilitated  con- 
ditions, 171 
Anticoagulants,  90 
Antithrombin,  11 
Atropin,  36 

Banti's  disease,  226,  228 
Benign  hemorrhages,  159 
Benzol  poisoning,  transfusion 

in,  230 
Bernheim's  method,  97,  124 

technic,  98 
Bleeders,  7,  13,  203 
Bleeding,  3,  4,  6, 7, 15,  208 
accidental,  6 
armamentarium    for 

treating,    40 
caused      by      duodenal 

ulcer,  44 
control  of,  34,  44 
control       of       original 

source,  152 
difficulties     encountered 
in  deciding  when  the 
actual    limit    of,    has 
been  reached,  169 
gastric,  9 

intestinal,  9,  10,  159 
invisible,  14 
measures  to  stop,  38 
249 


250 


INDEX 


Bleeding  from  nasal  opera- 
tion, 7 

phenomenon  of,  1 

post-operative,  160 

postpartum,  164 

spontaneous,     14,    202, 
210 

from  tooth  extraction,  7 

uterine,  4,  8 

vicarious,  9 
Blood,  abnormality  in,  11 

changes   following  sple- 
nectomy, 191 

coagulation  of,  1, 2,  4,  6, 
10,  11,  41 

defibrinated,      used      in 
transfusion,  56 

derangements  of,  2 

disease,   transfusion   in, 
51 

dosage,  171,  178 

average  size,  178 

examination  of,  2 

findings,  in  acute  hemor- 
rhage, 29 

in  hemorrhage,   19 

flow,  difficulty  of  judg- 
ing    amount     of     in 
transfusion,  105 
duration       of       in 
transfusion,   100 

fresh  human,  206 

groups,  73 

lack  of  platelets  in,  10 

loss,  1,  3,  6,  15,  201 


Blood    loss,    individuals    af- 
fected by,  149 
in  childbirth,  147 
minor  disturbances  of,  2 
not    advisable    to    keep, 

141 
per    cent,    of,    in    total 

body  weight,  147 
and  the  phenomenon  of 

bleeding,  1 
realization  of  therapeu- 
tic usefulness  of,  80 
regeneration,  2 
relatives,  73,  79 
transfusion  therapy,  ex- 
panding field  of,  172 
Blood-pressure  for  guidance, 

43 
Brain  centres,  150 
Brem's  method  of  group  test- 
ing, 238 

technic,  239 
simplification    of    Moss' 
group  method,  233 
Bullet  wounds,  151 

Cacodylates,  172 
Cassarean  section,  168 
Calcium,  11 
Calcium  lactate  in  jaundice, 

220 
of  doubtful  value  as 

a     prophylactic, 

37 
use  of,  49 
Camphorated  oil,  36 


INDEX 


251 


Cannulas,  113 

Cheyne-Stokes   form   of   res- 
piration developed,  39 
Child-birth,   psychic   element 

lacking  in,  148 
Citrate  method  of  transfusing 
blood,  109,  112, 
153 
the  present  method 
of  election,  145 
technic    of   transfusion, 
58 
Citrated   blood   for  transfu- 
sion, 141 
therapeutic    action 
of,  142 
Clots   in    needles    and    tubes 

during  transfusion,  61 
Coagulation,  41,  202,  207 

adding  chemicals  to  the 

blood  to  retard,  58 
fresh  human   blood   ex- 
erts   beneficial    effect 
on,  158 
prevention  of,  89 
Crile's  method,  90 
observations,  30 
tube,  87 
"  Cumulative  bleeding,"  167 

Danger  to  donor,  82 

of   transmitting  disease 
by  transfusion,  62 
Dangers  of  transfusion,  53, 
58,  63 


Debilitated  conditions,  trans- 
fusions for,  52 
Defibrinated    blood    used    in 

transfusion,  56 
Diagnosis     between     hemor- 
rhage and  like  conditions, 
32, 
Diagnoses  of  hemorrhage,  17 
Differential  diagnosis,  24 
Digitalis,  36 

Direct  method,  drawbacks  to, 
88 
transfusion,  87,  90 

two-tube  method  of, 
153 
Donor,  dangers  to,  77,  82 
meaning  of  the  term,  77 
the  paid,  80 
selection  of,  77 
temperament  of,  79 
treatment     of     after 

transfusion,  77 
welfare  of,  107 
Donors,  professional,  80,  81 

suitable,  68 
Drugs,  futility  of,  35 
Duodenal      ulcer,      bleeding 

caused  by,  44 
Duration   of   actual   flow   in 
transfusion,  106 

Eclampsia,  transfusion  in, 
230 

Ectopic  pregnancy,  rup- 
tured, 162 

Elsberg's  method,  94 


252 


INDEX 


Embolus  during  transfusion, 

61 
Exsanguinating,  the  term  as 

used,  47 

Factors  that  enter  into  cal- 
culation of  bulk,  106 

Gastric  bleedings,  9 

ulcer,  29,  154,  156 

Haematoma,  formation  of,  en- 
courages infection,  161 
Haemoglobin,  diagnosis  of,  64 
Haemoglobinuria,  65,  64 
Haemolysis,  53,  55,  63,  66,  69 
change  of  sentiment  con- 
cerning, 67 
fatal  case  of,  82 
prevention  of,  by  tests, 

65 
test  for,  80,  241,  244 
Hemolytic     and     agglutina- 
tion tests  in  blood  trans- 
fusion, 233 
Haemophilia,  11,  12,  48,  202 
serum  therapy  in,  205 
transfusion  in,  54,  201 
treatment  of,  205 
Haemophiliacs,  7,  13 
Heart  collapse,  24,  27 

overdistention  of,  68 
in  transfusion,  59 
Hemorrhage,  1, 16 
accidental,  151 
acute,  blood  findings  in, 
29 


Hemorrhage,    acute,    danger 
of,  170 
blood  findings  in,  19 
concealed,  3,  5 
control  of,  34 
diagnosis  of,  17 
intensive  study  of  neg- 
lected, 34 
intra-abdominal,  3,  4 
intra-cranial,  4 
post-operative,  4 
pulmonary,  3 
renal,  10 

study  made  possible  as 
result  of  blood  trans- 
fusion, 40 
subcutaneous,  10 
symptoms  of,  18 
tabulation  of,  3,  5 
tentative  plan  of  proced- 
ure in,  41 
traumatic,  49 
unconcealed,  3,  5 
of  violence,  7 
Hemorrhages,  benign,  169 
exsanguinating,   8,    14, 

47 
intestinal,  159 
Hemorrhagic  conditions, 
transfusions    for    the 
relief  of,  51 
diseases,  10,  14,  201 
Hirudin,   failure   of   for  hu- 
mans, 90 
Horse     serum      in     general 
valueless      for     checking 
bleeding,  37 


INDEX 


253 


Human  serum  losing  favor,  37 
use  of,  206 
tissue       for       checking 
bleeding,  37 

Icteric    conditions,    bleeding 

in,  219 
Icterus,  14 

Idiopathic  anaemia,  182 
Illuminating   gas    poisoning, 

transfusion  in,  230 
Indirect         anti-coagulation 
method,  90 
method,  first,  108 

latest,  109 
transfusion,  87,  108 
whole  blood  method,  90 
Individuals  affected  by  blood 

loss,  149 
Industrial  accidents,  151 
Infection  in  transfusion 
through  faulty  technic,  61 
Infections,  transfusion  in,  51 
Instrument  used  in  Unger's 

method,  119 
Instruments  for  transfusion, 

111 
Intestinal   bleeding,    9,    159, 
173 
hemorrhages,  159 
Intoxications,      transfusions 

in,  51 
Iodine  technic,  61 

Jaundice,  219 

bleeding  in,  48,  219 
calcium  lactate  in,  220 


Jaundice,    liver    changes    in, 
221 
obstructive  type  of,  222 
transfusion  in,  201 

of  whole  blood  in, 
220 
Kephalin,  208,  209 
Kimpton-Brown  method,  111 
as  modified  by  Beth 
Vincent,  127 
Krumbhaar's  conclusions  re- 
garding       pernicious 
anaemia,  197 
paper    on    splenectomy, 
188 
Latest    indirect    method    of 

transfusing  blood,  109 
Leukaemia,  14,  226 

acute  lymphatic,  226 
futility    of    transfusion 

in,  228 
transfusion  in,  226 
Lewisohn's  method,  90 

method    of    sodium    cit- 
rate transfusion,  139 
Ligation  of  a  bleeding  point 

to  stop  hemorrhage,  157 
Lindeman's  method,  89,  113 
needle  and  syringe,  112 
Longitudinal  sinus,  injection 
of  blood  into,  213 

Macroscopic  hsemoglobinuria, 

53 
Malaria       transmitted       by 

means   of  transfusion,  63 


i54 


INDEX 


Melaena  neonatorum,  210 

subcutaneous       in- 
jection of  whole 
blood  in,  211 
subcutaneous  injec- 
tion of  fresh  hu- 
man    serum     in, 
211 
transfusion  in,  4)8, 
49,  201,  210 
Menopause,  9 
Menstruation,  4,  6 
Method     of    transfusion     in 
hemorrhagic  disease  of  the 
newborn,  134 
Morphia,    depressant    effect 
on     respiration     and 
blood-pressure,  38 
effect  on  blood-pressure 

84 
indicated  to  quiet  rest- 
lessness, 37 
Morphine  administered  in  in- 
testinal bleeding,  36 
Moss'  method,  technic,  234 
of  grouping  bloods 
for    transfusion, 
233 
of    group    testing, 
233 
Multiple  transfusions,  85 

Nasal     operation,     bleeding 

from,  7 
Nausea  in  transfusion,  60 


Newborn,  method  of  trans- 
fusion in  hemorrhagic  dis- 
ease of  the,  134 

Nose-bleeding,  7 

Novocaine,  99 

Obstetricians  complacent  in 
case  of  hemorrhage,  164 

Operating,  refinements  of,  28 

Operation  for  transfusion, 
114 

Ooze,  cases  of  protracted,  205 

Pahcreatitis,  acute,  as  pos- 
sible when  hemorrhage  is 
suspected,  29 
Paraffined  glass  cylinder 
used  in  collecting  blood, 
109 
Patients,    public    ward    and 

private,  48 
Percentage  study  worked  out 
for    the    four    groups    of 
blood,  74 
Peritonitis,  streptococcus,  23 
Pernicious   anaemia,   Krumb- 
haar's       conclu- 
sions   regarding, 
197 
outlook  in,  185 
remissions  in,  185 
size  of  spleen  in,  192 
splenectomy  in,  190 
transfusion  in,  172, 
186 
Placenta,  premature  separa- 
tion of,  168 


INDEX 


i55 


Placenta    praevia,  154 

praevia,  bleeding,  166 
Platelet  count  of  haemophil- 
iac blood,  204 
Platelets,  absence  of,  10,  215, 

218 
Poisoning,  transfusion  in,  51 
Post-operative  bleeding,  160 
hemorrhage,        transfu- 
sion in,  54 
prostration,  transfusion 
in,  175 
Postpartum  bleeding,  164 
hemorrhage,       probable 
cause  of,  165 
Post-transfusion        reaction, 

143 
Preliminary  tests,  66,  69 
Prevention  of  hiemolysis   by 

tests,  65 
Primary  pernicious   anaemia, 

181 
Professional  donors,  80,  81 
Prothrombin,  11 
lack  of,  203 
Psychic  element,  148 

lacking     in     child- 
birth, 148 
Pulmonary  hemorrhages,  3 
Purpura,  10,  214 

etiology  of,  215 
therapy  of,  215 
transfusion  in,  201,  214, 
217 
Purpuric  spots,  215 


Habbit   serum    for   checking 
bleeding,  37 

Radial  dissection,  99 

Reaction   following   transfu- 
sion, 144 
post-transfusion,  143 

Recipient,    meaning    of    the 
term,  77 

Red    blood-cells    in    antemia, 
184 

Renal  hemorrhages,  10 

Remissions  in  pernicious  anae- 
mia, 185 

Routine  in  transfusion,  105 

Ruptured  ectopic  pregnancy, 
162 

Salt  solution,  abuse  of,  35 

caution    needed    in 

using,  40 
in  gastric  ulcer,  156 
lack    of    sustaining 

power  of,  40 
too  much  expected 
of,  38 
Secondary  anaemias,  171 
Sera  as  remedies  for  check- 
ing bleeding,  37 
Serum,  injection  of,  49 

therapy,  206 
Shock,  24,  148 
causes  of,  27 
defined,  27 

from  loss  of  blood,  42 
transfusion  in,  147 


256 


INDEX 


Simon's    method    of    testing 
out  donors,  233 
test    for    agglutination 
and  haemolysis,  241 
Sinus  operation,  bleeding  in, 

7 
Sodium  citrate,  90,  109 
action  of,  137 
transfusion,    Lewi- 
sohn's  method  of, 
139 
Spleen,  size  of,  in  pernicious 

anaemia,  192 
Splenectomy,  181,  187 

blood  changes  following, 

191 
bone-marrow  in,  196 
mortality  of,  189 
in     pernicious     anaemia, 

187,  190 
prognosis  in,  196 
Splenic  anaemia,  226,  228 
Spontaneous  bleeding,  14 
Stab  wounds,  151 
Stethoscope     for     detecting 
early  cardiac  distress,  60 
Streptococcus         peritonitis, 

2S 
Subcutaneous  hemorrhage,  10 
Sugar    solution    in    gastric 

ulcer,  156 
Surgical    operations,    trans- 
fusions in  connection  with, 
50 
Sydenstricker's     method     of 
testing  out  donors,  233 


Sydenstricker's  test  for  haeiiv- 
olysis    and    agglutination, 

Syphilis  as  a  cause  of  melena 
neonatorum,  210 
transmitted  by  means  of 
transfusion,  62 

Tests  for  compatibility,  68 
for  predicting  haemolysis 
and  agglutination,  72 
preliminary,  66,  69 
prevention  by,  65 
"  Therapeutic  possibilities  of 
transfusion ;  "  paper  read, 
171,  186 
Thrombin,  11 

Thrombokinase,  lack  of,  203 
Thromboplastin,  11 
Tissue  extract  for  checking 

bleeding,  37 
Tooth    extraction,    bleeding 

from,  7 
Toxaemia,  229 

of     pregnancy,     trans- 
fusion in,  230 
Toxaemias,  226 
Transfusion  in  actual  hemor- 
rhage, 50 
in  acute  blood  loss,  169 
in  acute  hemorrhage, 
147 
advisability  of,  49 
in     anaemic     conditions, 

171 
beginning  of,  87 


INDEX 


257 


Transfusion  in  blood  disease, 
51 
citrate  method  of,  109, 
145 
technic  of,  58 
citrated  blood  for,  141 
in  connection  with  sur- 
gical operations,  50 
danger  of  transmitting 

disease  by,  62 
dangers  of,  53,  58,  63 
in  debilitated  conditions, 

52,  171 
direct,  87,  90,  153 
duration  of  actual  flow 

in,  106 
emergency,  8 
evolution  of,  46,  47 
first  indirect  method  of, 

108 
for  the  relief  of  hemor- 
rhagic conditions,  51 
heart  in,  59 
in  haemophilia,  201 
in   hemorrhagic    disease 

of  the  newborn,  134 
in  illuminating  gas  poi- 
soning, 230 
indications  for,  46,  48 
indirect,  87,  90, 108, 109 
in  infections,  51 
in  intoxications,  51 
in  jaundice,  201 
latest    indirect    method, 
109 


Transfusion  in  melaena  neona- 
torum, 201,  210 

methods  of,  87 

more  widespread  use  of, 
58 

nausea  in,  60 

operation  for,  114 

in  pernicious  anaemia, 
172,  186 

in  poisoning,  51 

in  post-operative  pros- 
tration, 175 

procrastination  in,  42 

in  purpura,  201,  214 

reaction  following,  144? 

routine  in,  105 

selection  of  donor  for, 
77 

70  mm.  of  mercury  indi- 
cation for  immediate, 
45 

in  shock,  147 

syphilis  transmitted  by 
means  of,  62 

technic,  87 

as  a  therapeutic  agent, 
171 

tube,  two-piece,  213 

in  tuberculosis,  54 

whole,    untreated    blood 
for,  141 
Transfusions  in  the  home.  111 

multiple,  85 
Tuberculosis,  transfusion  in, 
54 


258 


INDEX 


Two-tube  method,  153  , 
Typhoid  bleeding,  154 

Unger's  method,  118 
Uterine  bleedings,  4,  8 

Volcanic  gastric  ulcers,  154 

Wassermann  test,  80 

test  for  donor  in  trans- 
fusion, 62 


Welfare  of  donor,  107 
Whole    blood,    subcutaneous 
injection  of,  49 
therapeutic    action 

of,  142 
transfusion     of    in 

jaundice,  220 
used  in  transfusion, 
56 
untreated    blood    for 
transfusion,  141 


INDEX  TO  REFERENCES 


Agote,  L,  145 
Balfour,  D.  C,  198 
Barker,  L.  R,  33 
Bernheim,  B.  M.,  15,  45,  52, 

75,  145,  170,  180 
Bigland,  A.  D.,  180 
Bloodgood,  J.  C,  45 
Brem,  W.  V.,  75,  145,  239 
Brown,  J.  H.,  146 
Bunting,  C.  H.,  231 
Burmeister,  W.  H.,  231 
Cecil,  H.  L.,  223 
Cherry,  T.  H.,  75 
Comminskey,  L.  J.  J,,  225 
Crile,  G.  W.,  33,  45, 145, 170 
Curtis,  A.  H.,  45,  145,  170 
David,  V.  C,  45,  145,  170 
Davis,  J.  D.,  180 
Decastello,  A.,  199 
Duke,  W.  W.,  223 
Dunn,  G.  R.,  75 
Elsberg,  C.  A.,  145 
Ely,  A.  H.,  231 


Emsheimer,  H.  W.,  223 
Eppinger,  H.,  199 
Ewing,  E.  M.,  33 
Friedman,  S.  S.,  76 
Gettler,  A.  O.,  231 
Hahn,  M.,  223 
Helmholz,  H.  F.,  145,  223 
Hess,  A.  F.,  224 
Hirschfeld,  H.,  199 
Hirschf elder,  A.  D.,  33 
Hooker,  R.  S.,  146 
Howell,  W.  H.,  15,  224 
Huber,  D.  R.  C,  199 
Janeway,  H.  H.,  33 
Kaliski,  D.  J.,  76 
Keator,  H.  M.,  231 
Kimpton,  A.  R.,  146 
Klemperer,  G.,  199 
Krumbhaar,  E.  B.,  199 
Lambert,  S.  W.,  224 
Langrock,  E.  G.,  75 
Lee,  R.  I.,  16,  199,  225 
Lespinasse,  V.  D.,  224 


INDEX 


259 


Levinson,  L.  L.,  170 
Lewisohn,  R.,  146 
Libman,  E.,  52,  146, 174, 180 
Lindeman,  E.,  75,  146,  231 
Litchfield,  L.,  45 
McClure,  R.  D.,  75,  199,  232 
McCrae,  T.,  33 
McCurdy,  U.  F.,  200 
Mayo,  W.  J.,  33,  170,  231 
Miller,  G.,  52 
Minot,  G.  R.,  76,  241 
Moffitt,  H.  C,  199 
Morawitz,  P.,  15,  86 
Moss,  W.  L.,  76,  224 
Musser,  J.  H.,  199 
Osier,  Sir  W.,  33 
Ottenberg,  R.,  52,  76,  146, 

180,  224,  231 
Packard,  M.,  231 
Peck,  C.  H.,  224 
Peterson,  E.  W.,   170,   180, 

224 
Pool,  E.  H.,  232 
Ranzi,  E.,  199 
Richardson,  E.  H.,  170 
Robertson,  O.,  199 


Roblee,  W.  N.,  200 
Rodman,  J.  S.,  232 
Sahli,  H.,  225 
Salant,  W.,  146 
Satterlee,  H.  S.,  146 
Schlenker,  L.,  225 
Schloss,  C.  M.,  225 
Schmidt,  P.,  86 
Schwarz,  H.,  224 
Simon,  C.  E.,  16 
StUlman,  R.  G.,  232 
Thompson,  J.  E.,  33, 170 
Turk,  W.,  200 
Unger,  L.,  225 
linger,  L.  J.,  146 
Vander  Hoof,  D.,  200 
Vincent,  B.,  16, 146, 199, 212, 

225 
Vogel,  K.  M.,  200 
Weil,  R.,  146 
Welch,  J.  E.,  225 
Whipple,  G.  H.,  16,  225 
WiUard,  F.  P.,  232 
Wise,  L.  E.,  146 
Yates,  J.  L.,  231 
Zucker,  T.  F.,  225 


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